The importance of RNA structure in RNA editing and a potential proofreading mechanism for correct guide RNA:pre-mRNA binary complex formation

Journal of Molecular Biology
Daniel E Golden, S L Hajduk

Abstract

RNA editing in trypanosomes is a post-transcriptional process responsible for correcting the coding sequences of many mitochondrial mRNAs. Uridine bases are specifically added or deleted from mRNA by an enzymatic cascade in which a pre-edited mRNA is cleaved specifically, uridine bases are added or removed, and the corrected mRNA is ligated. The process is directed by RNA molecules, termed guide RNAs (gRNA). The ability of this class of small, non-coding RNA to function in RNA editing is essential for these organisms. Typically, gRNAs are transcribed independent of their cognate mRNA and anneal to form a binary RNA complex. An exception from this process is the cytochrome oxidase subunit II (COII) mRNA, which encodes its gRNA within its 3' untranslated region. This gRNA lacks the ability to function in trans. Using an in vitro editing assay, we find that improving thermodynamic stability to the anchor region through increased Watson-Crick base-pairing is sufficient to impart trans editing activity. We further show that a point mutation outside the known functional regions of a gRNA induces both a conformational rearrangement of the gRNA and causes a decrease in the rate of editing. Taken together, these results lead us to propo...Continue Reading

References

Jun 1, 1992·Molecular and Cellular Biology·M HarrisS Hajduk
Aug 25, 1995·Nucleic Acids Research·B SchmidH U Göringer
Feb 7, 1997·The Journal of Biological Chemistry·J KöllerH U Göringer
Jun 15, 1997·Nucleic Acids Research·T HermannH U Göringer
Oct 10, 1997·Nucleic Acids Research·J D AlfonzoL Simpson
Jan 16, 1999·Nucleic Acids Research·S S Leung, D J Koslowsky
Apr 17, 1999·The Journal of Biological Chemistry·M L Hayman, L K Read
Jan 12, 2001·Molecular and Cellular Biology·J Cruz-ReyesB Sollner-Webb
Mar 17, 2001·The EMBO Journal·U F MüllerH U Göringer
Sep 21, 2001·Molecular and Cellular Biology·A K PanigrahiK D Stuart
Jan 15, 2002·Nucleic Acids Research·Ulrich F Müller, H Ulrich Göringer
Feb 13, 2002·Molecular and Cellular Biology·Robert P IgoKenneth Stuart
Mar 23, 2002·Cell·Susan Madison-AntenucciStephen L Hajduk
Jul 26, 2002·Molecular Microbiology·Kenneth Stuart, Aswini K Panigrahi
Mar 22, 2003·RNA·Aswini K PanigrahiKenneth Stuart
Jun 25, 2003·Molecular Cell·Nancy Lewis ErnstKenneth Stuart
Jul 9, 2004·Biophysical Journal·Roumen A Dimitrov, Michael Zuker
Feb 5, 2005·Trends in Biochemical Sciences·Kenneth D StuartAswini K Panigrahi
Jun 28, 2005·Nucleic Acids Research·Nicholas R Markham, Michael Zuker
Nov 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jason CarnesKenneth Stuart

❮ Previous
Next ❯

Citations

Oct 24, 2007·Molecular and Cellular Biology·Jason CarnesKenneth Stuart
Sep 3, 2010·PloS One·Larissa ReifurDonna J Koslowsky
Feb 26, 2010·Journal of Biomedicine & Biotechnology·Toya Nath Baral

❮ Previous
Next ❯

Related Concepts

Related Feeds

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.