The RNA chaperone activity of the Trypanosoma brucei editosome raises the dynamic of bound pre-mRNAs

Scientific Reports
W-Matthias LeederH U Göringer

Abstract

Mitochondrial transcript maturation in African trypanosomes requires an RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. The reaction is catalyzed by editosomes and requires guide (g)RNAs as templates. Recent data demonstrate that the binding of pre-edited mRNAs to editosomes is followed by a chaperone-type RNA remodeling reaction. Here we map the changes in RNA folding using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). We demonstrate that pre-mRNAs in their free state adopt intricately folded, highly stable 2D-structures. Editosome binding renders the pre-mRNAs to adopt 2D-conformations of reduced stabilities. On average about 30% of the nucleotides in every pre-mRNA are affected with a prevalence for U-nucleotides. The data demonstrate that the chaperone activity acts by increasing the flexibility of U-residues to lower their base-pairing probability. This results in a simplified RNA folding landscape with a reduced energy barrier to facilitate the binding of gRNAs. The data provide a first rational for the enigmatic U-specificity of the editing reaction.

References

Sep 8, 1995·The Journal of Biological Chemistry·D Herschlag
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·H U GöringerK Stuart
Oct 2, 1998·FEBS Letters·J L MergnyL Lacroix
Jan 15, 2002·Nucleic Acids Research·Ulrich F Müller, H Ulrich Göringer
Jun 26, 2003·Nucleic Acids Research·Ivo L Hofacker
Jul 31, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peter Tompa, Peter Csermely
Mar 24, 2005·Journal of the American Chemical Society·Edward J MerinoKevin M Weeks
Sep 15, 2005·Nucleic Acids Research·Jean-Louis MergnyJonathan B Chaires
Jul 29, 2006·Journal of Molecular Biology·Gregory BokinskyXiaowei Zhuang
Mar 21, 2007·Journal of the American Chemical Society·Stefanie A Mortimer, Kevin M Weeks
Apr 25, 2007·Nucleic Acids Research·Warren A Kibbe
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Rick Russell
Mar 19, 2008·RNA Biology·Lukas RajkowitschRenée Schroeder
Dec 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Katherine E DeiganKevin M Weeks
Mar 17, 2010·BMC Bioinformatics·Jessica S Reuter, David H Mathews
Jun 18, 2010·Methods : a Companion to Methods in Enzymology·Justin T Low, Kevin M Weeks
Nov 4, 2010·RNA Biology·Sarah A Woodson
Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Feng LiLarry Simpson
Feb 18, 2012·Nature·Elizabeth A DethoffHashim M Al-Hashimi
Apr 6, 2012·Journal of the American Chemical Society·Jennifer L McGinnisKevin M Weeks
Apr 11, 2012·Wiley Interdisciplinary Reviews. RNA·Stefania MillevoiStéphan Vagner
Jun 5, 2012·The Journal of Biological Chemistry·Cordula BöhmH Ulrich Göringer
Sep 22, 2012·Annual Review of Microbiology·H Ulrich Göringer
Mar 9, 2013·Science·Jacob K GrohmanKevin M Weeks
Mar 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christine E HajdinKevin M Weeks
Apr 17, 2013·Biochimica Et Biophysica Acta·Elisabeth KruseH Ulrich Göringer
Dec 18, 2013·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Ronny LorenzPeter F Stadler
Jan 21, 2014·Biochimie·Ruslan Aphasizhev, Inna Aphasizheva
Feb 14, 2014·Nature·Hajin KimSarah A Woodson
May 16, 2014·Nucleic Acids Research·Prakash ShresthaHanbin Mao
Dec 30, 2014·Biopolymers·Kevin M Weeks
Aug 1, 2015·FEBS Letters·Anna CzerwoniecJanusz M Bujnicki

❮ Previous
Next ❯

Citations

Jul 31, 2018·Nucleic Acids Research·Christin VoigtH Ulrich Göringer
Dec 14, 2018·Nucleic Acids Research·Brady TravisMaria A Schumacher
Apr 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Franck Dumetz, Catherine J Merrick
Jul 13, 2017·Journal of Nucleic Acids·W-Matthias LeederH Ulrich Göringer

❮ Previous
Next ❯

Methods Mentioned

BETA
acylation
in vitro transcription
size exclusion chromatography
electrophoresis

Software Mentioned

RNAstructure
SHAPEfinder
OligoCalc
ViennaRNA
ShapeKnots
SHAPE

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.