PPR polyadenylation factor defines mitochondrial mRNA identity and stability in trypanosomes
| Autor: | Takuma Suematsu, Ruslan Aphasizhev, Liye Zhang, Lan Huang, François M. Sement, Inna Aphasizheva, Stefano Monti, Tian Yu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Polyadenylation Trypanosoma brucei brucei Protozoan Proteins RNA-binding protein Biology Ribosome General Biochemistry Genetics and Molecular Biology 03 medical and health sciences RNA Precursors Guide RNA RNA Processing Post-Transcriptional Molecular Biology Polymerase Messenger RNA General Immunology and Microbiology General Neuroscience Articles Molecular biology Mitochondria Cell biology 030104 developmental biology RNA editing biology.protein Pentatricopeptide repeat |
| Zdroj: | The EMBO Journal. 36:2435-2454 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.201796808 |
| Popis: | In Trypanosoma brucei , most mitochondrial mRNAs undergo internal changes by RNA editing and 3′ end modifications. The temporally separated and functionally distinct modifications are manifested by adenylation prior to editing, and by post‐editing extension of a short A‐tail into a long A/U‐heteropolymer. The A‐tail stabilizes partially and fully edited mRNAs, while the A/U‐tail enables mRNA binding to the ribosome. Here, we identify an essential pentatricopeptide repeat‐containing RNA binding protein, kinetoplast polyadenylation factor 3 (KPAF3), and demonstrate its role in protecting pre‐mRNA against degradation by the processome. We show that KPAF3 recruits KPAP1 poly(A) polymerase to the 3′ terminus, thus leading to pre‐mRNA stabilization, or decay depending on the occurrence and extent of editing. In vitro , KPAF3 stimulates KPAP1 activity and inhibits mRNA uridylation by RET1 TUTase. Our findings indicate that KPAF3 selectively directs pre‐mRNA toward adenylation rather than uridylation, which is a default post‐trimming modification characteristic of ribosomal and guide RNAs. As a quality control mechanism, KPAF3 binding ensures that mRNAs entering the editing pathway are adenylated and, therefore, competent for post‐editing A/U‐tailing and translational activation. |
| Databáze: | OpenAIRE |
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