Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter April 29, 2020

The piRNA pathway in planarian flatworms: new model, new insights

Iana V. Kim , Sebastian Riedelbauch and Claus-D. Kuhn ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that associate with members of the PIWI clade of the Argonaute superfamily of proteins. piRNAs are predominantly found in animal gonads. There they silence transposable elements (TEs), regulate gene expression and participate in DNA methylation, thus orchestrating proper germline development. Furthermore, PIWI proteins are also indispensable for the maintenance and differentiation capabilities of pluripotent stem cells in free-living invertebrate species with regenerative potential. Thus, PIWI proteins and piRNAs seem to constitute an essential molecular feature of somatic pluripotent stem cells and the germline. In keeping with this hypothesis, both PIWI proteins and piRNAs are enriched in neoblasts, the adult stem cells of planarian flatworms, and their presence is a prerequisite for the proper regeneration and perpetual tissue homeostasis of these animals. The piRNA pathway is required to maintain the unique biology of planarians because, in analogy to the animal germline, planarian piRNAs silence TEs and ensure stable genome inheritance. Moreover, planarian piRNAs also contribute to the degradation of numerous protein-coding transcripts, a function that may be critical for neoblast differentiation. This review gives an overview of the planarian piRNA pathway and of its crucial function in neoblast biology.

Acknowledgments

We are grateful to Elizabeth M. Duncan from the University of Kentucky (Lexington, KY, USA) for comments on this manuscript. We thank Caroline Rossignol for contributing to artwork. Moreover, we are grateful to Labib Rouhana from Wright State University (Dayton, OH, USA) and to an anonymous reviewer for the insightful comments that significantly improved our manuscript. This work was supported by the Elite Network of Bavaria, the University of Bayreuth, and the Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers (to C.-D.K).

  1. Funding: Elitenetzwerk Bayern, Funder Id: http://dx.doi.org/10.13039/501100008848, Grant Number: N-BM-2013-244.

References

Abnave, P., Mottola, G., Gimenez, G., Boucherit, N., Trouplin, V., Torre, C., Conti, F., Amara, A.B., Lepolard, C., Djian, B., et al. (2014). Screening in Planarians Identifies MORN2 as a Key Component in LC3-Associated Phagocytosis and Resistance to Bacterial Infection. Cell Host Microbe 16, 338–350.10.1016/j.chom.2014.08.002Search in Google Scholar

Almazan, E.M.P., Lesko, S.L., Markey, M.P., and Rouhana, L. (2018). Girardia dorotocephala transcriptome sequence, assembly, and validation through characterization of piwi homologs and stem cell progeny markers. Dev. Biol. 433, 433–447.10.1016/j.ydbio.2017.07.022Search in Google Scholar

Altincicek, B. and Vilcinskas, A. (2008). Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris. Front. Zool. 5, 6.10.1186/1742-9994-5-6Search in Google Scholar

Andersen, P.R., Tirian, L., Vunjak, M., and Brennecke, J. (2017). A heterochromatin-dependent transcription machinery drives piRNA expression. Nature 549, 54–59.10.1038/nature23482Search in Google Scholar

Aravin, A.A., Naumova, N.M., Tulin, A.V., Vagin, V.V., Rozovsky, Y.M., and Gvozdev, V.A. (2001). Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr. Biol. 11, 1017–1027.10.1016/S0960-9822(01)00299-8Search in Google Scholar

Aravin, A., Gaidatzis, D., Pfeffer, S., Lagos-Quintana, M., Landgraf, P., Iovino, N., Morris, P., Brownstein, M.J., Kuramochi-Miyagawa, S., Nakano, T., et al. (2006). A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207.10.1038/nature04916Search in Google Scholar PubMed

Aravin, A.A., Sachidanandam, R., Girard, A., Toth, K.F., and Hannon, G.J. (2007). Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316, 744–747.10.1126/science.1142612Search in Google Scholar PubMed

Aravin, A.A., Sachidanandam, R., Bourc’his, D., Schaefer, C., Pezic, D., Toth, K.F., Bestor, T., and Hannon, G.J. (2008). A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31, 785–799.10.1016/j.molcel.2008.09.003Search in Google Scholar PubMed PubMed Central

Arkhipova, I.R. and Yushenova, I.A. (2019). Giant transposons in eukaryotes: is bigger better? Genome Biol. Evol. 11, 906–918.10.1093/gbe/evz041Search in Google Scholar PubMed PubMed Central

Arnold, C.P., Merryman, M.S., Harris-Arnold, A., McKinney, S.A., Seidel, C.W., Loethen, S., Proctor, K.N., Guo, L., and Alvarado, A.S. (2016). Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38. eLife 5, e16793.10.7554/eLife.16793.029Search in Google Scholar

Ashe, A., Sapetschnig, A., Weick, E.-M., Mitchell, J., Bagijn, M.P., Cording, A.C., Doebley, A.-L., Goldstein, L.D., Lehrbach, N.J., Pen, J.L., et al. (2012). piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150, 88–99.10.1016/j.cell.2012.06.018Search in Google Scholar PubMed PubMed Central

Barckmann, B., Pierson, S., Dufourt, J., Papin, C., Armenise, C., Port, F., Grentzinger, T., Chambeyron, S., Baronian, G., Desvignes, J.-P., et al. (2015). Aubergine iCLIP reveals piRNA-dependent decay of mRNAs involved in germ cell development in the early embryo. Cell Rep. 12, 1205–1216.10.1016/j.celrep.2015.07.030Search in Google Scholar PubMed PubMed Central

Batki, J., Schnabl, J., Wang, J., Handler, D., Andreev, V.I., Stieger, C.E., Novatchkova, M., Lampersberger, L., Kauneckaite, K., Xie, W., et al. (2019). The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation. Nat. Struct. Mol. Biol. 26, 720–731.10.1038/s41594-019-0270-6Search in Google Scholar PubMed PubMed Central

Brennecke, J., Aravin, A.A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., and Hannon, G.J. (2007). Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128, 1089–1103.10.1016/j.cell.2007.01.043Search in Google Scholar PubMed

Brown, D.D.R. and Pearson, B.J. (2017). A brain unfixed: unlimited neurogenesis and regeneration of the adult planarian nervous system. Front. Neurosci. 11, 289.10.3389/fnins.2017.00289Search in Google Scholar PubMed PubMed Central

Cai, P., Piao, X., Hou, N., Liu, S., Wang, H., and Chen, Q. (2012). Identification and characterization of argonaute protein, Ago2 and its associated small RNAs in Schistosoma japonicum. PLoS Negl. Trop. Dis. 6, 1745–1745.10.1371/journal.pntd.0001745Search in Google Scholar PubMed PubMed Central

Carmell, M.A., Girard, A., van de Kant, H.J.G., Bourc’his, D., Bestor, T.H., de Rooij, D.G., and Hannon, G.J. (2007). MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev. Cell 12, 503–514.10.1016/j.devcel.2007.03.001Search in Google Scholar PubMed

Chalvet, F., Teysset, L., Terzian, C., Prud’homme, N., Santamaria, P., Bucheton, A., and Pélisson, A. (1999). Proviral amplification of the Gypsy endogenous retrovirus of Drosophila melanogaster involves env-independent invasion of the female germline. EMBO J. 18, 2659–2669.10.1093/emboj/18.9.2659Search in Google Scholar PubMed PubMed Central

Clark, J.P. and Lau, N.C. (2014). Piwi Proteins and piRNAs step onto the systems biology stage. Adv. Exp. Med. Biol. 825, 159–197.10.1007/978-1-4939-1221-6_5Search in Google Scholar PubMed PubMed Central

Collins, J.J. (2017). Platyhelminthes. Curr. Biol. 27, R252–R256.10.1016/j.cub.2017.02.016Search in Google Scholar PubMed

Coward, S.J. (1974). Chromatoid bodies in somatic cells of the planarian: observations on their behavior during mitosis. Anat. Rec. 180, 533–545.10.1002/ar.1091800312Search in Google Scholar PubMed

Cox, D.N., Chao, A., Baker, J., Chang, L., Qiao, D., and Lin, H. (1998). A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 12, 3715–3727.10.1101/gad.12.23.3715Search in Google Scholar PubMed PubMed Central

Czech, B., Munafò, M., Ciabrelli, F., Eastwood, E.L., Fabry, M.H., Kneuss, E., and Hannon, G.J. (2018). piRNA-guided genome defense: from biogenesis to silencing. Annu. Rev. Genet. 52, 131–157.10.1146/annurev-genet-120417-031441Search in Google Scholar PubMed

Dai, P., Wang, X., Gou, L.-T., Li, Z.-T., Wen, Z., Chen, Z.-G., Hua, M.-M., Zhong, A., Wang, L., Su, H., et al. (2019). A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis. Cell 179, 1566–158110.1016/j.cell.2019.11.022Search in Google Scholar PubMed PubMed Central

Davies, E.L., Lei, K., Seidel, C.W., Kroesen, A.E., McKinney, S.A., Guo, L., Robb, S.M., Ross, E.J., Gotting, K., and Alvarado, A.S. (2017). Embryonic origin of adult stem cells required for tissue homeostasis and regeneration. Elife 6, e21052.10.7554/eLife.21052Search in Google Scholar PubMed PubMed Central

Dennis, C., Zanni, V., Brasset, E., Eymery, A., Zhang, L., Mteirek, R., Jensen, S., Rong, Y.S., and Vaury, C. (2013). Dot COM, a nuclear transit center for the primary piRNA pathway in Drosophila. PLoS One 8, 1–6.10.1371/journal.pone.0072752Search in Google Scholar PubMed PubMed Central

Duc, C., Yoth, M., Jensen, S., Mouniée, N., Bergman, C.M., Vaury, C., and Brasset, E. (2019). Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion. Genome Biol. 20, 127.10.1186/s13059-019-1736-xSearch in Google Scholar PubMed PubMed Central

Duncan, E.M., Chitsazan, A.D., Seidel, C.W., and Alvarado, A.S. (2015). Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo. Cell Rep. 13, 2741–2755.10.1016/j.celrep.2015.11.059Search in Google Scholar PubMed PubMed Central

Egger, B., Gschwentner, R., and Rieger, R. (2006). Free-living flatworms under the knife: past and present. Dev. Genes Evol. 217, 89–104.10.1007/s00427-006-0120-5Search in Google Scholar PubMed PubMed Central

Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498.10.1038/35078107Search in Google Scholar PubMed

Fabry, M.H., Ciabrelli, F., Munafo, M., Eastwood, E.L., Kneuss, E., Falciatori, I., Falconio, F.A., Hannon, G.J., and Czech, B. (2019). piRNA-guided co-transcriptional silencing coopts nuclear export factors. Elife 8, e47999.10.7554/eLife.47999Search in Google Scholar PubMed PubMed Central

Fernandéz-Taboada, E., Moritz, S., Zeuschner, D., Stehling, M., Schöler, H.R., Saló, E., and Gentile, L. (2010). Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation. Development 137, 1055–1065.10.1242/dev.042564Search in Google Scholar PubMed

Fincher, C.T., Wurtzel, O., de Hoog, T., Kravarik, K.M., and Reddien, P.W. (2018). Cell type transcriptome atlas for the planarian Schmidtea mediterranea. Science 360, 6391.10.1126/science.aaq1736Search in Google Scholar PubMed PubMed Central

Friedländer, M.R., Adamidi, C., Han, T., Lebedeva, S., Isenbarger, T.A., Hirst, M., Marra, M., Nusbaum, C., Lee, W.L., Jenkin, J.C., et al. (2009). High-resolution profiling and discovery of planarian small RNAs. Proc. Natl. Acad. Sci. U.S.A. 106, 11546–11551.10.1073/pnas.0905222106Search in Google Scholar PubMed PubMed Central

Gainetdinov, I., Colpan, C., Arif, A., Cecchini, K., and Zamore, P.D. (2018). A single mechanism of biogenesis, initiated and directed by PIWI proteins, explains piRNA production in most animals. Mol. Cell 71, 775–790.10.1016/j.molcel.2018.08.007Search in Google Scholar PubMed PubMed Central

Gan, H., Lin, X., Zhang, Z., Zhang, W., Liao, S., Wang, L., and Han, C. (2011). piRNA profiling during specific stages of mouse spermatogenesis. RNA 17, 1191–1203.10.1261/rna.2648411Search in Google Scholar PubMed PubMed Central

Girard, A., Sachidanandam, R., Hannon, G.J., and Carmell, M.A. (2006). A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442, 199–202.10.1038/nature04917Search in Google Scholar PubMed

Goriaux, C., Desset, S., Renaud, Y., Vaury, C., and Brasset, E. (2014). Transcriptional properties and splicing of the flamenco piRNA cluster. EMBO Rep. 15, 411–418.10.1002/embr.201337898Search in Google Scholar PubMed PubMed Central

Gou, L.-T., Dai, P., Yang, J.-H., Xue, Y., Hu, Y.-P., Zhou, Y., Kang, J.-Y., Wang, X., Li, H., Hua, M.-M., et al. (2014). Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 24, 680–700.10.1038/cr.2014.41Search in Google Scholar PubMed PubMed Central

Gou, L.-T., Kang, J.-Y., Dai, P., Wang, X., Li, F., Zhao, S., Zhang, M., Hua, M.-M., Lu, Y., Zhu, Y., et al. (2017). Ubiquitination-deficient mutations in human Piwi cause male infertility by impairing histone-to-protamine exchange during spermiogenesis. Cell 169, 1090–1104.10.1016/j.cell.2017.04.034Search in Google Scholar PubMed PubMed Central

Grivna, S.T., Beyret, E., Wang, Z., and Lin, H. (2006). A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 20, 1709–1714.10.1101/gad.1434406Search in Google Scholar PubMed PubMed Central

Grohme, M.A., Schloissnig, S., Rozanski, A., Pippel, M., Young, G.R., Winkler, S., Brandl, H., Henry, I., Dahl, A., Powell, S., et al. (2018). The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms. Nature 554, 56–61.10.1038/nature25473Search in Google Scholar PubMed PubMed Central

Gunawardane, L.S., Saito, K., Nishida, K.M., Miyoshi, K., Kawamura, Y., Nagami, T., Siomi, H., and Siomi, M.C. (2007). A Slicer-mediated mechanism for repeat-associated siRNA 5′end formation in Drosophila. Science 315, 1587–1590.10.1126/science.1140494Search in Google Scholar PubMed

Guo, T., Peters, A.H.F.M., and Newmark, P.A. (2006). A Bruno-like gene is required for stem cell maintenance in planarians. Dev. Cell 11, 159–169.10.1016/j.devcel.2006.06.004Search in Google Scholar PubMed

Hagstrom, D., Cochet-Escartin, O., and Collins, E.-M.S. (2016). Planarian brain regeneration as a model system for developmental neurotoxicology. Regeneration 3, 65–77.10.1002/reg2.52Search in Google Scholar PubMed PubMed Central

Han, B.W., Wang, W., Li, C., Weng, Z., and Zamore, P.D. (2015). piRNA-guided transposon cleavage initiates Zucchini-dependent, phased piRNA production. Science 348, 817–821.10.1126/science.aaa1264Search in Google Scholar PubMed PubMed Central

Hayashi, T. and Agata, K. (2018). A subtractive FACS method for isolation of planarian stem cells and neural cells. Methods Mol. Biol. 1774, 467–478.10.1007/978-1-4939-7802-1_19Search in Google Scholar PubMed

Hayashi, R., Schnabl, J., Handler, D., Mohn, F., Ameres, S.L., and Brennecke, J. (2016). Genetic and mechanistic diversity of piRNA 3′-end formation. Nature 539, 588–592.10.1038/nature20162Search in Google Scholar PubMed PubMed Central

Homolka, D., Pandey, R.R., Goriaux, C., Brasset, E., Vaury, C., Sachidanandam, R., Fauvarque, M.-O., and Pillai, R.S. (2015). PIWI slicing and RNA elements in precursors instruct directional primary piRNA biogenesis. Cell Rep. 12, 418–428.10.1016/j.celrep.2015.06.030Search in Google Scholar PubMed

Horwich, M.D., Li, C., Matranga, C., Vagin, V., Farley, G., Wang, P., and Zamore, P.D. (2007). The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr. Biol. 17, 1265–1272.10.1016/j.cub.2007.06.030Search in Google Scholar PubMed

Houwing, S., Kamminga, L.M., Berezikov, E., Cronembold, D., Girard, A., van den Elst, H., Filippov, D.V., Blaser, H., Raz, E., Moens, C.B., et al. (2007). A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in zebrafish. Cell 129, 69–82.10.1016/j.cell.2007.03.026Search in Google Scholar PubMed

Hughes, T., Ekman, D., Ardawatia, H., Elofsson, A., and Liberles, D.A. (2007). Evaluating dosage compensation as a cause of duplicate gene retention in Paramecium tetraurelia. Genome Biol 8, 213.10.1186/gb-2007-8-5-213Search in Google Scholar PubMed PubMed Central

Ivankovic, M., Haneckova, R., Thommen, A., Grohme, M.A., Vila-Farré, M., Werner, S., and Rink, J.C. (2019). Model systems for regeneration: planarians. Development 146, 17.10.1242/dev.167684Search in Google Scholar PubMed

Iwasaki, Y.W., Murano, K., Ishizu, H., Shibuya, A., Iyoda, Y., Siomi, M.C., Siomi, H., and Saito, K. (2016). Piwi modulates chromatin accessibility by regulating multiple factors including histone H1 to repress transposons. Mol. Cell 63, 408–419.10.1016/j.molcel.2016.06.008Search in Google Scholar PubMed

Izumi, N., Shoji, K., Sakaguchi, Y., Honda, S., Kirino, Y., Suzuki, T., Katsuma, S., and Tomari, Y. (2016). Identification and functional analysis of the pre-piRNA 3′ Trimmer in silkworms. Cell 164, 962–973.10.1016/j.cell.2016.01.008Search in Google Scholar PubMed PubMed Central

Juliano, C.E., Swartz, S.Z., and Wessel, G.M. (2010). A conserved germline multipotency program. Development 137, 4113–4126.10.1242/dev.047969Search in Google Scholar PubMed PubMed Central

Juliano, C., Wang, J., and Lin, H. (2011). Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu. Rev. Genet. 45, 447–469.10.1146/annurev-genet-110410-132541Search in Google Scholar PubMed PubMed Central

Juliano, C.E., Reich, A., Liu, N., Götzfried, J., Zhong, M., Uman, S., Reenan, R.A., Wessel, G.M., Steele, R.E., and Lin, H. (2014). PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. Proc. Natl. Acad. Sci. U.S.A. 111, 337–342.10.1073/pnas.1320965111Search in Google Scholar PubMed PubMed Central

Kashima, M., Kumagai, N., Agata, K., and Shibata, N. (2016). Heterogeneity of chromatoid bodies in adult pluripotent stem cells of planarian Dugesia japonica. Dev. Growth Differ. 58, 225–237.10.1111/dgd.12268Search in Google Scholar PubMed

Kashima, M., Agata, K., and Shibata, N. (2018). Searching for non-transposable targets of planarian nuclear PIWI in pluripotent stem cells and differentiated cells. Dev. Growth Differ. 15, 433–418.10.1111/dgd.12536Search in Google Scholar PubMed

Kawaoka, S., Hara, K., Shoji, K., Kobayashi, M., Shimada, T., Sugano, S., Tomari, Y., Suzuki, Y., and Katsuma, S. (2013). The comprehensive epigenome map of piRNA clusters. Nucl. Acids Res 41, 1581–1590.10.1093/nar/gks1275Search in Google Scholar PubMed PubMed Central

Kazazian, H.H. (2004). Mobile elements: drivers of genome evolution. Science 303, 1626–1632.10.1126/science.1089670Search in Google Scholar PubMed

Kim, K.W. (2019). PIWI proteins and piRNAs in the nervous system. Mol. Cell 42, 828–835.Search in Google Scholar

Kim, K.W., Tang, N.H., Andrusiak, M.G., Wu, Z., Chisholm, A.D., and Jin, Y. (2018). A neuronal piRNA pathway inhibits axon regeneration in C. elegans. Neuron 97, 511–519.10.1016/j.neuron.2018.01.014Search in Google Scholar PubMed PubMed Central

Kim, I.V., Duncan, E.M., Ross, E.J., Gorbovytska, V., Nowotarski, S.H., Elliott, S.A., Alvarado, A.S., and Kuhn, C.-D. (2019a). Planarians recruit piRNAs for mRNA turnover in adult stem cells. Genes Dev. 33, 1575–1590.10.1101/gad.322776.118Search in Google Scholar PubMed PubMed Central

Kim, I.V., Ross, E.J., Dietrich, S., Döring, K., Alvarado, A.S., and Kuhn, C.-D. (2019b). Efficient depletion of ribosomal RNA for RNA sequencing in planarians. BMC Genomics 20, 909–912.10.1186/s12864-019-6292-ySearch in Google Scholar PubMed PubMed Central

Kirino, Y. and Mourelatos, Z. (2007). Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′ termini. Nat. Struct. Mol. Biol. 14, 347–348.10.1038/nsmb1218Search in Google Scholar PubMed

Klattenhoff, C., Xi, H., Li, C., Lee, S., Xu, J., Khurana, J.S., Zhang, F., Schultz, N., Koppetsch, B.S., Nowosielska, A., et al. (2009). The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell 138, 1137–1149.10.1016/j.cell.2009.07.014Search in Google Scholar PubMed PubMed Central

Labbé, R.M., Irimia, M., Currie, K.W., Lin, A., Zhu, S.J., Brown, D.D.R., Ross, E.J., Voisin, V., Bader, G.D., Blencowe, B.J., et al. (2012). A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals. Stem Cells 30, 1734–1745.10.1002/stem.1144Search in Google Scholar PubMed PubMed Central

Lai, A.G. and Aboobaker, A.A. (2018). EvoRegen in animals: time to uncover deep conservation or convergence of adult stem cell evolution and regenerative processes. Dev. Biol. 433, 118–131.10.1016/j.ydbio.2017.10.010Search in Google Scholar PubMed

Lau, N.C., Seto, A.G., Kim, J., Kuramochi-Miyagawa, S., Nakano, T., Bartel, D.P., and Kingston, R.E. (2006). Characterization of the piRNA complex from rat testes. Science 313, 363–367.10.1126/science.1130164Search in Google Scholar PubMed

Lau, N.C., Robine, N., Martin, R., Chung, W.-J., Niki, Y., Berezikov, E., and Lai, E.C. (2009). Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res. 19, 1776–1785.10.1101/gr.094896.109Search in Google Scholar PubMed PubMed Central

Lee, H.-C., Gu, W., Shirayama, M., Youngman, E., Jr, D.C., and Mello, C.C. (2012). C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 150, 78–87.10.1016/j.cell.2012.06.016Search in Google Scholar PubMed PubMed Central

Lehmann, R. (2012). Germline stem cells: origin and destiny. Cell Stem Cell 10, 729–739.10.1016/j.stem.2012.05.016Search in Google Scholar PubMed PubMed Central

Leuschner, P.J.F., Ameres, S.L., Kueng, S., and Martinez, J. (2006). Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7, 314–320.10.1038/sj.embor.7400637Search in Google Scholar PubMed PubMed Central

Lewis, S.H., Quarles, K.A., Yang, Y., Tanguy, M., Frézal, L., Smith, S.A., Sharma, P.P., Cordaux, R., Gilbert, C., Giraud, I., et al. (2018). Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements. Nat. Ecol. Evol. 2, 174–181.10.1038/s41559-017-0403-4Search in Google Scholar PubMed PubMed Central

Li, C., Vagin, V.V., Lee, S., Xu, J., Ma, S., Xi, H., Seitz, H., Horwich, M.D., Syrzycka, M., Honda, B.M., et al. (2009). Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137, 509–521.10.1016/j.cell.2009.04.027Search in Google Scholar PubMed PubMed Central

Li, Y.-Q., Zeng, A., Han, X.-S., Wang, C., Li, G., Zhang, Z.-C., Wang, J.-Y., Qin, Y.-W., and Jing, Q. (2011). Argonaute-2 regulates the proliferation of adult stem cells in planarian. Cell Res. 21, 1750–1754.10.1038/cr.2011.151Search in Google Scholar PubMed PubMed Central

Li, X.Z., Roy, C.K., Dong, X., Bolcun-Filas, E., Wang, J., Han, B.W., Xu, J., Moore, M.J., Schimenti, J.C., Weng, Z., et al. (2013). An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol. Cell 50, 67–81.10.1016/j.molcel.2013.02.016Search in Google Scholar PubMed PubMed Central

Lim, A.K. and Kai, T. (2007). Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 104, 6714–6719.10.1073/pnas.0701920104Search in Google Scholar PubMed PubMed Central

Lin, H. and Spradling, A.C. (1997). A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 124, 2463–2476.10.1242/dev.124.12.2463Search in Google Scholar PubMed

Madeira, F., Park, Y.M., Lee, J., Buso, N., Gur, T., Madhusoodanan, N., Basutkar, P., Tivey, A.R.N., Potter, S.C., Finn, R.D., et al. (2019). The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucl. Acids Res. 47, 636–641.10.1093/nar/gkz268Search in Google Scholar PubMed PubMed Central

Malone, C.D., Brennecke, J., Dus, M., Stark, A., McCombie, W.R., Sachidanandam, R., and Hannon, G.J. (2009). Specialized piRNA pathways act in germline and somatic tissues of the drosophila ovary. Cell 137, 522–535.10.1016/j.cell.2009.03.040Search in Google Scholar PubMed PubMed Central

Matsumoto, N., Nishimasu, H., Sakakibara, K., Nishida, K.M., Hirano, T., Ishitani, R., Siomi, H., Siomi, M.C., and Nureki, O. (2016). Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA. Cell 167, 484–497.10.1016/j.cell.2016.09.002Search in Google Scholar PubMed

Medina, R., Ghule, P.N., Cruzat, F., Barutcu, A.R., Montecino, M., Stein, J.L., van Wijnen, A.J., and Stein, G.S. (2012). Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle. Mol. Cell Biol. 32, 3860–3871.10.1128/MCB.00736-12Search in Google Scholar PubMed PubMed Central

Miesen, P., Girardi, E., and van Rij, R.P. (2015). Distinct sets of PIWI proteins produce arbovirus and transposon-derived piRNAs in Aedes aegypti mosquito cells. Nucl. Acids Res. 43, 6545–6556.10.1093/nar/gkv590Search in Google Scholar PubMed PubMed Central

Mitchell, A.L., Attwood, T.K., Babbitt, P.C., Blum, M., Bork, P., Bridge, A., Brown, S.D., Chang, H.-Y., El-Gebali, S., Fraser, M.I., et al. (2018). InterPro in 2019: improving coverage, classification and access to protein sequence annotations. Nucl. Acids Res. 47, D351–D360.10.1093/nar/gky1100Search in Google Scholar PubMed PubMed Central

Mohn, F., Sienski, G., Handler, D., and Brennecke, J. (2014). The Rhino-Deadlock-Cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in Drosophila. Cell 157, 1364–1379.10.1016/j.cell.2014.04.031Search in Google Scholar PubMed

Mohn, F., Handler, D., and Brennecke, J. (2015). piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis. Science 348, 812–817.10.1126/science.aaa1039Search in Google Scholar PubMed PubMed Central

Mulder, K.D., Kuales, G., Pfister, D., Willems, M., Egger, B., Salvenmoser, W., Thaler, M., Gorny, A.-K., Hrouda, M., Borgonie, G., et al. (2009). Characterization of the stem cell system of the acoel Isodiametra pulchra. BMC Dev. Biol. 9, 69.10.1186/1471-213X-9-69Search in Google Scholar PubMed PubMed Central

Murano, K., Iwasaki, Y.W., Ishizu, H., Mashiko, A., Shibuya, A., Kondo, S., Adachi, S., Suzuki, S., Saito, K., Natsume, T., et al. (2019). Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing. EMBO J. 38, e102870.10.15252/embj.2019102870Search in Google Scholar PubMed PubMed Central

Nakagawa, H., Ishizu, H., Hasegawa, R., Kobayashi, K., and Matsumoto, M. (2012). Drpiwi-1 is essential for germline cell formation during sexualization of the planarian Dugesia ryukyuensis. Dev. Biol. 361, 167–176.10.1016/j.ydbio.2011.10.014Search in Google Scholar PubMed

Nandi, S., Chandramohan, D., Fioriti, L., Melnick, A.M., Hébert, J.M., Mason, C.E., Rajasethupathy, P., and Kandel, E.R. (2016). Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain. Proc. Natl. Acad. Sci. U.S.A. 113, 12697–12702.10.1073/pnas.1609287113Search in Google Scholar PubMed PubMed Central

Newmark, P.A. and Alvarado, A.S. (2002). Not your father’s planarian: a classic model enters the era of functional genomics. Nat. Rev. Genet. 3, 210–219.10.1038/nrg759Search in Google Scholar PubMed

Ng, H.-H. and Surani, M.A. (2011). The transcriptional and signalling networks of pluripotency. Nat. Cell Biol. 13, 490–496.10.1038/ncb0511-490Search in Google Scholar PubMed

Nolde, M.J., Cheng, E.-C., Guo, S., and Lin, H. (2013). Piwi genes are dispensable for normal hematopoiesis in mice. PLoS One 8, 71950–71950.10.1371/journal.pone.0071950Search in Google Scholar PubMed PubMed Central

Ohara, T., Sakaguchi, Y., Suzuki, T., Ueda, H., Miyauchi, K., and Suzuki, T. (2007). The 3′ termini of mouse Piwi-interacting RNAs are 2′-O-methylated. Nat. Struct. Mol. Biol. 14, 349–350.10.1038/nsmb1220Search in Google Scholar PubMed

Önal, P., Grün, D., Adamidi, C., Rybak, A., Solana, J., Mastrobuoni, G., Wang, Y., Rahn, H.-P., Chen, W., Kempa, S., et al. (2012). Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells. EMBO J. 31, 2755–2769.10.1038/emboj.2012.110Search in Google Scholar PubMed PubMed Central

Ozata, D.M., Gainetdinov, I., Zoch, A., O’Carroll, D., and Zamore, P.D. (2019). PIWI-interacting RNAs: small RNAs with big functions. Nat. Rev. Genet. 20, 89–108.10.1038/s41576-018-0073-3Search in Google Scholar PubMed

Palakodeti, D., Smielewska, M., Lu, Y.C., Yeo, G.W., and Graveley, B.R. (2008). The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians. RNA 14, 1174–1186.10.1261/rna.1085008Search in Google Scholar PubMed PubMed Central

Peiris, T.H., Hoyer, K.K., and Oviedo, N.J. (2014). Innate immune system and tissue regeneration in planarians: an area ripe for exploration. Semin. Immunol. 26, 295–302.10.1016/j.smim.2014.06.005Search in Google Scholar PubMed PubMed Central

Pellettieri, J. (2019). Regenerative tissue remodeling in planarians – the mysteries of morphallaxis. Semin. Cell Dev. Biol. 87, 13–21.10.1016/j.semcdb.2018.04.004Search in Google Scholar PubMed PubMed Central

Perrat, P.N., DasGupta, S., Wang, J., Theurkauf, W., Weng, Z., Rosbash, M., and Waddell, S. (2013). Transposition-Driven Genomic Heterogeneity in the Drosophila Brain. Science 340, 91–95.10.1126/science.1231965Search in Google Scholar PubMed PubMed Central

Preall, J.B., Czech, B., Guzzardo, P.M., Muerdter, F., and Hannon, G.J. (2012). Shutdown is a component of the Drosophila piRNA biogenesis machinery. RNA 18, 1446–1457.10.1261/rna.034405.112Search in Google Scholar PubMed PubMed Central

Qi, H., Watanabe, T., Ku, H.-Y., Liu, N., Zhong, M., and Lin, H. (2011). The Yb body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells. J. Biol. Chem. 286, 3789–3797.10.1074/jbc.M110.193888Search in Google Scholar PubMed PubMed Central

Qiu, W., Guo, X., Lin, X., Yang, Q., Zhang, W., Zhang, Y., Zuo, L., Zhu, Y., Li, C.-S.R., Ma, C., et al. (2017). Transcriptome-wide piRNA profiling in human brains of Alzheimer’s disease. Neurobiol. Aging 57, 170–177.10.1016/j.neurobiolaging.2017.05.020Search in Google Scholar PubMed PubMed Central

Rajasethupathy, P., Antonov, I., Sheridan, R., Frey, S., Sander, C., Tuschl, T., and Kandel, E.R. (2012). A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149, 693–707.10.1016/j.cell.2012.02.057Search in Google Scholar PubMed PubMed Central

Ramat, A., Garcia-Silva, M.-R., Jahan, C., Naït-Saïdi, R., Dufourt, J., Garret, C., Chartier, A., Cremaschi, J., Patel, V., Decourcelle, M., et al. (2020). The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm. Cell Res. Biorxiv 859561. https://doi.org/10.1101/859561.10.1038/s41422-020-0294-9Search in Google Scholar PubMed PubMed Central

Rangan, P., Malone, C.D., Navarro, C., Newbold, S.P., Hayes, P.S., Sachidanandam, R., Hannon, G.J., and Lehmann, R. (2011). piRNA production requires heterochromatin formation in Drosophila. Curr. Biol. 21, 1373–1379.10.1016/j.cub.2011.06.057Search in Google Scholar PubMed PubMed Central

Reddien, P.W., Oviedo, N.J., Jennings, J.R., Jenkin, J.C., and Alvarado, A.S. (2005a). SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310, 1327–1330.10.1126/science.1116110Search in Google Scholar PubMed

Reddien, P.W., Bermange, A.L., Murfitt, K.J., Jennings, J.R., and Alvarado, A.S. (2005b). Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Dev. Cell 8, 635–649.10.1016/j.devcel.2005.02.014Search in Google Scholar PubMed PubMed Central

Rinkevich, Y., Rosner, A., Rabinowitz, C., Lapidot, Z., Moiseeva, E., and Rinkevich, B. (2010). Piwi positive cells that line the vasculature epithelium, underlie whole body regeneration in a basal chordate. Dev. Biol. 345, 94–104.10.1016/j.ydbio.2010.05.500Search in Google Scholar PubMed

Rinkevich, Y., Voskoboynik, A., Rosner, A., Rabinowitz, C., Paz, G., Oren, M., Douek, J., Alfassi, G., Moiseeva, E., Ishizuka, K.J., et al. (2013). Repeated, long-term cycling of putative stem cells between niches in a basal chordate. Dev. Cell 24, 76–88.10.1016/j.devcel.2012.11.010Search in Google Scholar PubMed PubMed Central

Rojas-Ríos, P. and Simonelig, M. (2018). piRNAs and PIWI proteins: regulators of gene expression in development and stem cells. Development 145, 17.10.1242/dev.161786Search in Google Scholar PubMed

Ross, R.J., Weiner, M.M., and Lin, H. (2014). PIWI proteins and PIWI-interacting RNAs in the soma. Nature 505, 353–359.10.1038/nature12987Search in Google Scholar PubMed PubMed Central

Rouget, C., Papin, C., Boureux, A., Meunier, A.-C., Franco, B., Robine, N., Lai, E.C., Pelisson, A., and Simonelig, M. (2010). Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 467, 1128–1132.10.1038/nature09465Search in Google Scholar PubMed PubMed Central

Rouhana, L., Shibata, N., Nishimura, O., and Agata, K. (2010). Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance. Dev. Biol. 341, 429–443.10.1016/j.ydbio.2010.02.037Search in Google Scholar PubMed

Rouhana, L., Vieira, A.P., Roberts-Galbraith, R.H., and Newmark, P.A. (2012). PRMT5 and the role of symmetrical dimethylarginine in chromatoid bodies of planarian stem cells. Development 139, 1083–1094.10.1242/dev.076182Search in Google Scholar PubMed PubMed Central

Rouhana, L., Weiss, J.A., King, R.S., and Newmark, P.A. (2014). PIWI homologs mediate Histone H4 mRNA localization to planarian chromatoid bodies. Development 141, 2592–2601.10.1242/dev.101618Search in Google Scholar PubMed PubMed Central

Roy, J., Sarkar, A., Parida, S., Ghosh, Z., and Mallick, B. (2017). Small RNA sequencing revealed dysregulated piRNAs in Alzheimer’s disease and their probable role in pathogenesis. Mol. Biosyst. 13, 565–576.10.1039/C6MB00699JSearch in Google Scholar PubMed

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J.M., Grohme, M.A., Hüttner, K., Bartscherer, K., Henry, I., and Rink, J.C. (2018). PlanMine 3.0 – improvements to a mineable resource of flatworm biology and biodiversity. Nucl. Acids Res. 47, 812–820.10.1093/nar/gky1070Search in Google Scholar PubMed PubMed Central

Saito, K., Nishida, K.M., Mori, T., Kawamura, Y., Miyoshi, K., Nagami, T., Siomi, H., and Siomi, M.C. (2006). Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev. 20, 2214–2222.10.1101/gad.1454806Search in Google Scholar PubMed PubMed Central

Saito, K., Sakaguchi, Y., Suzuki, T., Suzuki, T., Siomi, H., and Siomi, M.C. (2007). Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ ends. Genes Dev. 21, 1603–1608.10.1101/gad.1563607Search in Google Scholar PubMed PubMed Central

Salvetti, A., Rossi, L., Lena, A., Batistoni, R., Deri, P., Rainaldi, G., Locci, M.T., Evangelista, M., and Gremigni, V. (2005). DjPum, a homologue of Drosophila Pumilio, is essential to planarian stem cell maintenance. Development 132, 1863–1874.10.1242/dev.01785Search in Google Scholar PubMed

Seth, M., Shirayama, M., Gu, W., Ishidate, T., Conte Jr, D., and Mello, C.C. (2013). The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression. Dev. Cell 27, 656–663.10.1016/j.devcel.2013.11.014Search in Google Scholar PubMed PubMed Central

Shibata, N., Kashima, M., Ishiko, T., Nishimura, O., Rouhana, L., Misaki, K., Yonemura, S., Saito, K., Siomi, H., Siomi, M.C., et al. (2016). Inheritance of a nuclear PIWI from pluripotent stem cells by somatic descendants ensures differentiation by silencing transposons in planarian. Dev. Cell 37, 226–237.10.1016/j.devcel.2016.04.009Search in Google Scholar PubMed

Shirayama, M., Seth, M., Lee, H.-C., Gu, W., Ishidate, T., Jr, D.C., and Mello, C.C. (2012). piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 150, 65–77.10.1016/j.cell.2012.06.015Search in Google Scholar PubMed PubMed Central

Sienski, G., Dönertas, D., and Brennecke, J. (2012). Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 151, 964–980.10.1016/j.cell.2012.10.040Search in Google Scholar PubMed PubMed Central

Siomi, M.C., Mannen, T., and Siomi, H. (2010). How does the royal family of tudor rule the PIWI-interacting RNA pathway? Genes Dev 24, 636–646.10.1101/gad.1899210Search in Google Scholar PubMed PubMed Central

Skinner, D.E., Rinaldi, G., Suttiprapa, S., Mann, V.H., Smircich, P., Cogswell, A.A., Williams, D.L., and Brindley, P.J. (2012). Vasa-like DEAD-box RNA helicases of Schistosoma mansoni. PLoS Negl. Trop. Dis. 6, 1–11.10.1371/journal.pntd.0001686Search in Google Scholar PubMed PubMed Central

Skinner, D.E., Rinaldi, G., Koziol, U., Brehm, K., and Brindley, P.J. (2014). How might flukes and tapeworms maintain genome integrity without a canonical piRNA pathway? Trends Parasitol. 30, 123–129.10.1016/j.pt.2014.01.001Search in Google Scholar PubMed PubMed Central

Smit, A., Hubley, R., and Green, P. (2013). Repeatmasker Open-4.0. http://www.repeatmasker.org.Search in Google Scholar

Solana, J. (2013). Closing the circle of germline and stem cells: the Primordial Stem Cell hypothesis. Evodevo 4, 2.10.1186/2041-9139-4-2Search in Google Scholar PubMed PubMed Central

Solana, J., Lasko, P., and Romero, R. (2009). Spoltud-1 is a chromatoid body component required for planarian long-term stem cell self-renewal. Dev. Biol. 328, 410–421.10.1016/j.ydbio.2009.01.043Search in Google Scholar PubMed PubMed Central

Solana, J., Kao, D., Mihaylova, Y., Jaber-Hijazi, F., Malla, S., Wilson, R., and Aboobaker, A. (2012). Defining the molecular profile of planarian pluripotent stem cells using a combinatorial RNAseq, RNA interference and irradiation approach. Genome Biol. 13, R19.10.1186/gb-2012-13-3-r19Search in Google Scholar PubMed PubMed Central

Song, S.U., Kurkulos, M., Boeke, J.D., and Corces, V.G. (1997). Infection of the germ line by retroviral particles produced in the follicle cells: a possible mechanism for the mobilization of the gypsy retroelement of Drosophila. Development 124, 2789–2798.10.1242/dev.124.14.2789Search in Google Scholar PubMed

Sousa-Victor, P., Ayyaz, A., Hayashi, R., Qi, Y., Madden, D.T., Lunyak, V.V., and Jasper, H. (2017). Piwi is required to limit exhaustion of aging somatic stem cells. Cell Rep 20, 2527–2537.10.1016/j.celrep.2017.08.059Search in Google Scholar PubMed PubMed Central

Srivastava, M., Mazza-Curll, K.L., van Wolfswinkel, J.C., and Reddien, P.W. (2014). Whole-body acoel regeneration is controlled by Wnt and Bmp-Admp signaling. Curr. Biol. 24, 1107–1113.10.1016/j.cub.2014.03.042Search in Google Scholar PubMed

Stein, C.B., Genzor, P., Mitra, S., Elchert, A.R., Ipsaro, J.J., Benner, L., Sobti, S., Su, Y., Hammell, M., Joshua-Tor, L., et al. (2019). Decoding the 5′ nucleotide bias of PIWI-interacting RNAs. Nat. Commun. 10, 828.10.1038/s41467-019-08803-zSearch in Google Scholar PubMed PubMed Central

Sun, W., Samimi, H., Gamez, M., Zare, H., and Frost, B. (2018). Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies. Nat. Neurosci. 21, 1038–1048.10.1038/s41593-018-0194-1Search in Google Scholar PubMed PubMed Central

Swapna, L.S., Molinaro, A.M., Lindsay-Mosher, N., Pearson, B.J., and Parkinson, J. (2018). Comparative transcriptomic analyses and single-cell RNA sequencing of the freshwater planarian Schmidtea mediterranea identify major cell types and pathway conservation. Genome Biol. 19, 124.10.1186/s13059-018-1498-xSearch in Google Scholar PubMed PubMed Central

Tassetto, M., Kunitomi, M., Whitfield, Z.J., Dolan, P.T., Sánchez-Vargas, I., Garcia-Knight, M., Ribiero, I., Chen, T., Olson, K.E., and Andino, R. (2019). Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements. eLife 8, e41244.10.7554/eLife.41244.026Search in Google Scholar

Thomas, A.L., Rogers, A.K., Webster, A., Marinov, G.K., Liao, S.E., Perkins, E.M., Hur, J.K., Aravin, A.A., and Toth, K.F. (2013). Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 27, 390–399.10.1101/gad.209841.112Search in Google Scholar PubMed PubMed Central

Thomas, A.L., Toth, K.F., and Aravin, A.A. (2014). To be or not to be a piRNA: genomic origin and processing of piRNAs. Genome Biol. 15, 204.10.1186/gb4154Search in Google Scholar PubMed PubMed Central

Trost, T., Haines, J., Dillon, A., Mersman, B., Robbins, M., Thomas, P., and Hubert, A. (2018). Characterizing the role of SWI/SNF-related chromatin remodeling complexes in planarian regeneration and stem cell function. Stem Cell Res. 32, 91–103.10.1016/j.scr.2018.09.004Search in Google Scholar PubMed

Tsai, I.J., Zarowiecki, M., Holroyd, N., Garciarrubio, A., Sanchez-Flores, A., Brooks, K.L., Tracey, A., Bobes, R.J., Fragoso, G., Sciutto, E., et al. (2013). The genomes of four tapeworm species reveal adaptations to parasitism. Nature 496, 57–63.10.1038/nature12031Search in Google Scholar PubMed PubMed Central

Vagin, V.V., Sigova, A., Li, C., Seitz, H., Gvozdev, V., and Zamore, P.D. (2006). A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313, 320–324.10.1126/science.1129333Search in Google Scholar PubMed

Varjak, M., Dietrich, I., Sreenu, V.B., Till, B.E., Merits, A., Kohl, A., and Schnettler, E. (2018). Spindle-E acts antivirally against alphaviruses in mosquito cells. Viruses 10, 88.10.3390/v10020088Search in Google Scholar PubMed PubMed Central

Vila-Farré, M. and Rink, J.C. (2018). The ecology of freshwater planarians. Methods Mol. Biol. 1774, 173–205.10.1007/978-1-4939-7802-1_3Search in Google Scholar PubMed

Voronina, E., Seydoux, G., Sassone-Corsi, P., and Nagamori, I. (2011). RNA granules in germ cells. Cold Spring Harb. Perspect. Biol. 3, a002774.10.1101/cshperspect.a002774Search in Google Scholar PubMed PubMed Central

Wagner, D.E., Wang, I.E., and Reddien, P.W. (2011). Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332, 811–816.10.1126/science.1203983Search in Google Scholar PubMed PubMed Central

Wagner, D.E., Ho, J.J., and Reddien, P.W. (2012). Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell 10, 299–311.10.1016/j.stem.2012.01.016Search in Google Scholar PubMed PubMed Central

Wang, Y., Zayas, R.M., Guo, T., and Newmark, P.A. (2007). nanos function is essential for development and regeneration of planarian germ cells. Proc. Natl. Acad. Sci. U.S.A. 104, 5901–5906.10.1073/pnas.0609708104Search in Google Scholar PubMed PubMed Central

Wang, B., Collins, J.J.I., and Newmark, P.A. (2013). Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni. eLife 2, e00768.10.7554/eLife.00768Search in Google Scholar PubMed PubMed Central

Wang, W., Yoshikawa, M., Han, B.W., Izumi, N., Tomari, Y., Weng, Z., and Zamore, P.D. (2014). The initial uridine of primary piRNAs does not create the tenth adenine that Is the hallmark of secondary piRNAs. Mol. Cell 56, 708–716.10.1016/j.molcel.2014.10.016Search in Google Scholar PubMed PubMed Central

Wang, L., Dou, K., Moon, S., Tan, F.J., and Zhang, Z.Z. (2018). Hijacking oogenesis enables massive propagation of LINE and retroviral transposons. Cell 174, 1082–1094.e12.10.1016/j.cell.2018.06.040Search in Google Scholar PubMed PubMed Central

Wang, C., Yang, Z.-Z., Guo, F.-H., Shi, S., Han, X.-S., Zeng, A., Lin, H., and Jing, Q. (2019). Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea. J. Biol. Chem. 294, 9873–9887.10.1074/jbc.RA118.004445Search in Google Scholar PubMed PubMed Central

Watanabe, T., Takeda, A., Tsukiyama, T., Mise, K., Okuno, T., Sasaki, H., Minami, N., and Imai, H. (2006). Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev. 20, 1732–1743.10.1101/gad.1425706Search in Google Scholar PubMed PubMed Central

Wedeles, C.J., Wu, M.Z., and Claycomb, J.M. (2013). Protection of germline gene expression by the C. elegans Argonaute CSR-1. Dev. Cell 27, 664–671.10.1016/j.devcel.2013.11.016Search in Google Scholar PubMed

Wenemoser, D., Lapan, S.W., Wilkinson, A.W., Bell, G.W., and Reddien, P.W. (2012). A molecular wound response program associated with regeneration initiation in planarians. Genes Dev. 26, 988–1002.10.1101/gad.187377.112Search in Google Scholar PubMed PubMed Central

van Wolfswinkel, J.C. (2014). Piwi and potency: PIWI proteins in animal stem cells and regeneration. Integr. Comp. Biol. 54, 700–713.10.1093/icb/icu084Search in Google Scholar PubMed

van Wolfswinkel, J.C., Wagner, D.E., and Reddien, P.W. (2014). Single-cell analysis reveals functionally distinct classes within the planarian stem cell compartment. Cell Stem Cell 15, 326–339.10.1016/j.stem.2014.06.007Search in Google Scholar PubMed PubMed Central

Xiol, J., Spinelli, P., Laussmann, M.A., Homolka, D., Yang, Z., Cora, E., Couté, Y., Conn, S., Kadlec, J., Sachidanandam, R., et al. (2014). RNA clamping by Vasa assembles a piRNA amplifier complex on transposon transcripts. Cell 157, 1698–1711.10.1016/j.cell.2014.05.018Search in Google Scholar PubMed

Yamanaka, S., Siomi, M.C., and Siomi, H. (2014). piRNA clusters and open chromatin structure. Mobile DNA 5, 22.10.1186/1759-8753-5-22Search in Google Scholar PubMed PubMed Central

Yoshida-Kashikawa, M., Shibata, N., Takechi, K., and Agata, K. (2007). DjCBC-1, a conserved DEAD box RNA helicase of the RCK/p54/Me31B family, is a component of RNA-protein complexes in planarian stem cells and neurons. Dev. Dyn. 236, 3436–3450.10.1002/dvdy.21375Search in Google Scholar PubMed

Yu, T., Koppetsch, B.S., Pagliarani, S., Johnston, S., Silverstein, N.J., Luban, J., Chappell, K., Weng, Z., and Theurkauf, W.E. (2019). The piRNA response to retroviral invasion of the Koala genome. Cell 179, 632–643.10.1016/j.cell.2019.09.002Search in Google Scholar PubMed PubMed Central

Zeng, A., Li, Y.-Q., Wang, C., Han, X.-S., Li, G., Wang, J.-Y., Li, D.-S., Qin, Y.-W., Shi, Y., Brewer, G., et al. (2013). Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells. J. Cell Biol. 201, 409–425.10.1083/jcb.201207172Search in Google Scholar PubMed PubMed Central

Zeng, A., Li, H., Guo, L., Gao, X., McKinney, S., Wang, Y., Yu, Z., Park, J., Semerad, C., Ross, E., et al. (2018). Prospectively isolated tetraspanin+ neoblasts are adult pluripotent stem cells underlying planaria regeneration. Cell 173, 1593–1608.10.1016/j.cell.2018.05.006Search in Google Scholar PubMed

Zhang, Z., Xu, J., Koppetsch, B.S., Wang, J., Tipping, C., Ma, S., Weng, Z., Theurkauf, W.E., and Zamore, P.D. (2011). Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Mol. Cell 44, 572–584.10.1016/j.molcel.2011.10.011Search in Google Scholar PubMed PubMed Central

Zheng, Y. (2013). Phylogenetic analysis of the Argonaute protein family in platyhelminths. Mol. Phylogenet. Evol. 66, 1050–1054.10.1016/j.ympev.2012.11.014Search in Google Scholar PubMed

Zhou, X., Battistoni, G., Demerdash, O.E., Gurtowski, J., Wunderer, J., Falciatori, I., Ladurner, P., Schatz, M.C., Hannon, G.J., and Wasik, K.A. (2015). Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano. RNA 21, 1885–1897.10.1261/rna.052456.115Search in Google Scholar PubMed PubMed Central

Zhu, W., Pao, G.M., Satoh, A., Cummings, G., Monaghan, J.R., Harkins, T.T., Bryant, S.V., Voss, S.R., Gardiner, D.M., and Hunter, T. (2012). Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl. Dev. Biol. 370, 42–51.10.1016/j.ydbio.2012.07.021Search in Google Scholar PubMed PubMed Central

Zimmermann, L., Stephens, A., Nam, S.-Z., Rau, D., Kübler, J., Lozajic, M., Gabler, F., Söding, J., Lupas, A.N., and Alva, V. (2018). A completely reimplemented MPI bioinformatics toolkit with a new HHpred server at its core. J. Mol. Biol. 430, 2237–2243.10.1016/j.jmb.2017.12.007Search in Google Scholar PubMed

Received: 2019-12-23
Accepted: 2020-03-12
Published Online: 2020-04-29
Published in Print: 2020-09-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 8.12.2022 from https://www.degruyter.com/document/doi/10.1515/hsz-2019-0445/html
Scroll Up Arrow