Differential Binding of Mitochondrial Transcripts by MRB8170 and MRB4160 Regulates Distinct Editing Fates of Mitochondrial mRNA in Trypanosomes

0474329 - BC 2018 RIV US eng J - Journal Article
Dixit, Sameer - Mueller-McNicoll, M. - David, Vojtěch - Zarnack, K. - Ule, J. - Hashimi, Hassan - Lukeš, Julius
Differential Binding of Mitochondrial Transcripts by MRB8170 and MRB4160 Regulates Distinct Editing Fates of Mitochondrial mRNA in Trypanosomes.
mBio. Roč. 8, č. 1 (2017), č. článku e02288-16. ISSN 2161-2129. E-ISSN 2150-7511
R&D Projects: GA ČR GA15-21974S
Institutional support: RVO:60077344
Keywords : guide RNA * ribonucleoprotein complexes * nucleotide resolution * proteins * DNA * replication * tbrgg2 * subcomplexes * translation
OECD category: Biochemistry and molecular biology
Impact factor: 6.689, year: 2017

A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei. Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing. Integrating additional in vivo and in vitro data, we propose that binding of MRB8170 and/or MRB4160 onto pre-mRNA marks it for the initiation of editing and that initial binding of both proteins may facilitate the recruitment of other components of the RNA editing/processing machinery to ensure efficient editing. Surprisingly, MRB8170 also binds never-edited mRNAs, suggesting that at least this paralog has an additional role outside RNA editing to shape the mitochondrial transcriptome.
Permanent Link: http://hdl.handle.net/11104/0275076