Abstract
In eukaryotic cells, protein-coding sequences constitute a relatively small part of the genome. The rest of the genome is transcribed to non-coding RNAs (ncRNAs). Such RNAs form the cornerstone of a regulatory network that operates in parallel with the protein network. Their biological functions are based primarily on the ability to pair with and deactivate target messenger RNAs (mRNAs). To clarify the likely role of ncRNAs in complex genetic networks, we present and comprehensively analyze a kinetic model of one of the key counterparts of the network architectures. Specifically, the genes transcribed to ncRNAs are considered to interplay with a hierarchical two-layer set of genes transcribed to mRNAs. The genes forming the bottom layer are regulated from the top and negatively self-regulated. If the former regulation is positive, the dependence of the RNA populations on the governing parameters is found to be often non-monotonous. Specifically, the model predicts bistability. If the regulation is negative, the dependence of the RNA populations on the governing parameters is monotonous. In particular, the population of the mRNAs, corresponding to the genes forming the bottom layer, is nearly constant.
[1] F. Crick, Nature 227, 561 (1970) http://dx.doi.org/10.1038/227561a010.1038/227561a0Search in Google Scholar PubMed
[2] B. Alberts et al., Molecular Biology of the Cell (Garland, New York, 2002) Search in Google Scholar
[3] K. M. Herbert, W. J. Greenleaf, S. M. Block, Annu. Rev. Biochem. 77, 149 (2008) http://dx.doi.org/10.1146/annurev.biochem.77.073106.10074110.1146/annurev.biochem.77.073106.100741Search in Google Scholar PubMed PubMed Central
[4] J. T. Wade, K. Struhl, Curr. Opin. Genet. Dev. 18, 130 (2008) http://dx.doi.org/10.1016/j.gde.2007.12.00810.1016/j.gde.2007.12.008Search in Google Scholar PubMed PubMed Central
[5] N. J. Fuda, M. B. Ardehali, J. T. Lis, Nature 461, 186 (2009) http://dx.doi.org/10.1038/nature0844910.1038/nature08449Search in Google Scholar PubMed PubMed Central
[6] A. Korostelev, D. N. Ermolenko, H. F. Noller, Curr. Opin. Chem. Biol. 12, 674 (2008) http://dx.doi.org/10.1016/j.cbpa.2008.08.03710.1016/j.cbpa.2008.08.037Search in Google Scholar PubMed PubMed Central
[7] R. A. Marshall, C. E. Aitken, M. Dorywalska, J. D. Puglisi, Ann. Rev. Biochem. 77, 177 (2008) http://dx.doi.org/10.1146/annurev.biochem.77.070606.10143110.1146/annurev.biochem.77.070606.101431Search in Google Scholar PubMed
[8] J. B. Munro, K. Y. Sanbonmatsu, C. M. T. Spahn, S. C. Blanchard, Trends Biochem. Sci. 34, 390 (2009) http://dx.doi.org/10.1016/j.tibs.2009.04.00410.1016/j.tibs.2009.04.004Search in Google Scholar PubMed PubMed Central
[9] C. E. Holt, S. L. Bullock Science 326, 1212 (2009) http://dx.doi.org/10.1126/science.117648810.1126/science.1176488Search in Google Scholar PubMed PubMed Central
[10] H. D. Lipshitz, Nature Rev. Mol. Cell Bio. 10, 509 (2009) http://dx.doi.org/10.1038/nrm273010.1038/nrm2730Search in Google Scholar PubMed
[11] L. Shapiro, H. H. McAdams, R. Losick, Science 326, 1225 (2009) http://dx.doi.org/10.1126/science.117568510.1126/science.1175685Search in Google Scholar PubMed PubMed Central
[12] M. Kaern, T. C. Elston, W. J. Blake, J. J. Collins, Nature Rev. Genet. 6, 451 (2005) http://dx.doi.org/10.1038/nrg161510.1038/nrg1615Search in Google Scholar PubMed
[13] J. Paulsson, Phys. Life Rev. 2, 157 (2005) http://dx.doi.org/10.1016/j.plrev.2005.03.00310.1016/j.plrev.2005.03.003Search in Google Scholar
[14] G. Tiana, S. Krishna, S. Pigolotti, M. H. Jensen, K. Sneppen, Phys. Biol. 4, R1 (2007) http://dx.doi.org/10.1088/1478-3975/4/2/R0110.1088/1478-3975/4/2/R01Search in Google Scholar PubMed
[15] D. Kulasiri, L. K. Nguyen, S. Samarasinghe, Z. Xie, Curr. Bioinform. 3, 197 (2008) http://dx.doi.org/10.2174/15748930878590921410.2174/157489308785909214Search in Google Scholar
[16] A. Raj, A. van Oudenaarden, Cell 135, 216 (2008) http://dx.doi.org/10.1016/j.cell.2008.09.05010.1016/j.cell.2008.09.050Search in Google Scholar PubMed PubMed Central
[17] S. Bornholdt, Science 310, 449 (2005) http://dx.doi.org/10.1126/science.111995910.1126/science.1119959Search in Google Scholar PubMed
[18] G. Karlebach, R. Shamir, Nature Rev. Mol. Cell Bio. 9, 771 (2008) 10.1038/nrm2503Search in Google Scholar PubMed
[19] Y. Bar-Yam, D. Harmon, B. de Bivort, Science 323, 1016 (2009) http://dx.doi.org/10.1126/science.116322510.1126/science.1163225Search in Google Scholar PubMed
[20] M. C. Lagomarsino, B. Bassetti, G. Castellani, D. Remondini, Mol. Biosyst. 5, 335 (2009) http://dx.doi.org/10.1039/b816841p10.1039/b816841pSearch in Google Scholar PubMed
[21] T. R. Mercer, M. E. Dinger, J. S. Mattick, Nature Rev. Genet. 10, 155 (2009) http://dx.doi.org/10.1038/nrg252110.1038/nrg2521Search in Google Scholar PubMed
[22] J. Whitehead, G. K. Pandey, C. Kanduri, Biochim. Biophys. Acta 1790, 936 (2009) 10.1016/j.bbagen.2008.10.007Search in Google Scholar PubMed
[23] J. E. Wilusz, H. Sunwoo, D. L. Spector, Gene. Dev. 23, 1494 (2009) http://dx.doi.org/10.1101/gad.180090910.1101/gad.1800909Search in Google Scholar PubMed PubMed Central
[24] D. P. Bartel, Cell 136, 215 (2009) http://dx.doi.org/10.1016/j.cell.2009.01.00210.1016/j.cell.2009.01.002Search in Google Scholar PubMed PubMed Central
[25] M. Ghildiyal, P. D. Zamore, Nature Rev. Genet. 10, 94 (2009) http://dx.doi.org/10.1038/nrg250410.1038/nrg2504Search in Google Scholar PubMed PubMed Central
[26] V. N. Kim, J. Han, M. C. Siomi, Nature Rev. Mol. Cell. Bio. 10, (2009) 126. http://dx.doi.org/10.1038/nrm263210.1038/nrm2632Search in Google Scholar PubMed
[27] K. K. H. Farh et al., Science 310, 1817 (2005) http://dx.doi.org/10.1126/science.112115810.1126/science.1121158Search in Google Scholar PubMed
[28] E. Barbarotto, T. G. Schmittgen, G. A. Calin, Int. J. Cancer 122, 969 (2008) http://dx.doi.org/10.1002/ijc.2334310.1002/ijc.23343Search in Google Scholar PubMed
[29] F. C. Lynn, Trends Endocrin. Met. 20, 452 (2009) http://dx.doi.org/10.1016/j.tem.2009.05.00710.1016/j.tem.2009.05.007Search in Google Scholar PubMed
[30] J. Q. Yin, R. C. Zhao, K. V. Morris, Trends Biotechnol. 26, 70 (2008) http://dx.doi.org/10.1016/j.tibtech.2007.11.00710.1016/j.tibtech.2007.11.007Search in Google Scholar PubMed
[31] M. Selbach, B. Schwanhausser, N. Thierfelder, Z. Fang, R. Khanin, N. Rajewsky, Nature 455, 58 (2008) http://dx.doi.org/10.1038/nature0722810.1038/nature07228Search in Google Scholar PubMed
[32] D. Baek et al., Nature 455, 64 (2008) http://dx.doi.org/10.1038/nature0724210.1038/nature07242Search in Google Scholar PubMed PubMed Central
[33] A. Bethke, N. Fielenbach, Z. Wang, D. J. Mangelsdorf, A. Antebi, Science 324, 95 (2009) http://dx.doi.org/10.1126/science.116489910.1126/science.1164899Search in Google Scholar PubMed PubMed Central
[34] E. Levine, T. Hwa, Curr. Opin. Microbiol. 11, 574 (2008) http://dx.doi.org/10.1016/j.mib.2008.09.01610.1016/j.mib.2008.09.016Search in Google Scholar PubMed PubMed Central
[35] V. P. Zhdanov, Mol. Biosyst. 5, 638 (2009) http://dx.doi.org/10.1039/b808095j10.1039/b808095jSearch in Google Scholar PubMed
[36] V. P. Zhdanov, Biophysical Reviews and Letters 4, 267 (2009) http://dx.doi.org/10.1142/S179304800900103410.1142/S1793048009001034Search in Google Scholar
[37] V. P. Zhdanov, J. Phys. A-Math. Theor. 41, 285101 (2008) http://dx.doi.org/10.1088/1751-8113/41/28/28510110.1088/1751-8113/41/28/285101Search in Google Scholar
[38] V. P. Zhdanov, JETP Lett. 88, 466 (2008) http://dx.doi.org/10.1134/S002136400819012010.1134/S0021364008190120Search in Google Scholar
[39] V. P. Zhdanov, Biosystems 95, 75 (2009) http://dx.doi.org/10.1016/j.biosystems.2008.07.00210.1016/j.biosystems.2008.07.002Search in Google Scholar PubMed
[40] V. P. Zhdanov, Physica A 389, 887 (2010) http://dx.doi.org/10.1016/j.physa.2009.11.02810.1016/j.physa.2009.11.028Search in Google Scholar
[41] V. P. Zhdanov, Chem. Phys. Lett. 458, 359 (2008) http://dx.doi.org/10.1016/j.cplett.2008.04.11110.1016/j.cplett.2008.04.111Search in Google Scholar
[42] A. Nandi, C. Vaz, A. Bhattacharya, R. Ramaswamy, BMC Syst. Biol. 3, 45 (2009) http://dx.doi.org/10.1186/1752-0509-3-4510.1186/1752-0509-3-45Search in Google Scholar
[43] J. Shen, Z. Liu, W. Zheng, F. Xu, L. Chen, Physica A 388, 2995 (2009) http://dx.doi.org/10.1016/j.physa.2009.03.03210.1016/j.physa.2009.03.032Search in Google Scholar
[44] M. Aldana, Physica D 185, 45 (2003) http://dx.doi.org/10.1016/S0167-2789(03)00174-X10.1016/S0167-2789(03)00174-XSearch in Google Scholar
[45] H. -W. Ma, J. Buer, A. -P. Zeng, BMC Bioinformatics 5, 199 (2004) http://dx.doi.org/10.1186/1471-2105-5-19910.1186/1471-2105-5-199Search in Google Scholar PubMed PubMed Central
[46] A. Martynez-Antonio, S. C. Janga, D. Thieffry, J. Mol. Biol. 381, 238 (2008) http://dx.doi.org/10.1016/j.jmb.2008.05.05410.1016/j.jmb.2008.05.054Search in Google Scholar PubMed PubMed Central
[47] P. Guptasarma, Bioessays 17, 987 (1995) http://dx.doi.org/10.1002/bies.95017111210.1002/bies.950171112Search in Google Scholar PubMed
[48] S. Ghaemmaghami et al., Nature 425, 737 (2003) http://dx.doi.org/10.1038/nature0204610.1038/nature02046Search in Google Scholar PubMed
[49] M. Davidich, S. Bornholdt, J. Theor. Biol. 255, 269 (2008) http://dx.doi.org/10.1016/j.jtbi.2008.07.02010.1016/j.jtbi.2008.07.020Search in Google Scholar PubMed
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