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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

Online
ISSN
1437-4315
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Volume 388, Issue 7

Issues

Long-range impact of peripheral joining elements on structure and function of the hepatitis delta virus ribozyme

Rebecca A. Tinsley
  • 1Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109-1055, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nils G. Walter
  • 2Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109-1055, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2007-07-01 | DOI: https://doi.org/10.1515/BC.2007.088

Abstract

The HDV ribozyme is an RNA enzyme from the human pathogenic hepatitis delta virus (HDV) that has recently also been identified in the human genome. It folds into a compact, nested double-pseudoknot. We examined here the functional relevance of the capping loop L4 and the helical crossover J1/2, which tightly interlace the two helical stacks of the ribozyme. Peripheral structural elements such as these are present in cis-acting, but not trans-acting ribozymes, which may explain the order-of-magnitude decrease in cleavage activity observed in trans-acting ribozymes with promise in gene therapy applications. Comparison of a systematic set of cis- and trans-acting HDV ribozymes shows that the absence of either L4 or J1/2 significantly and independently impacts catalytic activity. Using terbium(III) footprinting and affinity studies, as well as distance measurements based on time-resolved fluorescence resonance energy transfer, we find that J1/2 is most important for conferring structural properties similar to those of the cis-acting ribozyme. Our results are consistent with a model in which removal of either a helical crossover or surprisingly a capping loop induces greater dynamics and expansion of the catalytic core at long range, impacting local and global folding, as well as catalytic function.

Keywords: gene therapy applications; global folding; RNA catalysis; terbium(III) footprinting; time-resolved FRET

About the article

Corresponding author


Received: 2007-02-18

Accepted: 2007-04-13

Published Online: 2007-07-01


Citation Information: Biological Chemistry, Volume 388, Issue 7, Pages 705–715, ISSN (Online) 14316730, ISSN (Print) 14374315, DOI: https://doi.org/10.1515/BC.2007.088.

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