A new way of understanding how RNA molecules may catalyze reactions central to retrovirus replication is presented in a paper published online in the new journal Nature Chemical Biology. The paper, by Joseph Piccirilli and colleagues, shows how a RNA molecule from the hepatitis delta virus (HDV) uses an acidic group to accelerate a chemical reaction central to its life cycle.
The active HDV molecule, or ribozyme, is a catalytic RNA molecule that cuts long RNAs into smaller chunks and is essential for the life cycle of the virus. The three-dimensional structure of the HDV ribozyme previously showed that a cytosine residue was positioned near the chemical reaction site. However, the role of the cytosine has remained mysterious for several years.
Piccirilli shows that catalytic RNAs, like protein enzymes, may use acidic groups to accelerate chemical reactions. By subtly changing the structure of the HDV ribozyme and measuring how each change affected its ability to chop up RNA, the team showed that the central cytosine base acts as a 'general acid' and donates a proton at a key step in the reaction.
This study suggests that RNA bases in ribozyme active sites may be more versatile than was previously thought.
Joseph A. Piccirilli (Howard Hughes Medical Institute, University of Chicago, IL, USA)
Additional contact for comment on paper:
Prof. Martha Fedor (The Scripps Research Institute, La Jolla, CA, USA)
Online publication can be accessed by clicking here.
About Nature Chemical Biology:
Launching in June 2005, Nature Chemical Biology is a new interdisciplinary journal that brings together the most innovative and important advances at the interface of biology and chemistry. This monthly journal will publish research from chemists who are applying the principles, language and tools of chemistry to biological systems and from biologists who seek to understand biological processes at the molecular level. Published in hard copy and online, the journal will include original research papers, supplemented with enhanced content including review articles, News & Views pieces, highlights from and correspondence with the chemical biology community, and commentaries on the field.
(C) Nature Chemical Biology press release.
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