期刊
EMBO JOURNAL
卷 36, 期 16, 页码 2435-2454出版社
WILEY
DOI: 10.15252/embj.201796808
关键词
pentatricopeptide repeat; polyadenylation; RNA editing; RNA stability; Trypanosoma
资金
- NIH [AI113157, AI091914, AI101057, GM074830, GM106003]
In Trypanosoma brucei, most mitochondrial mRNAs undergo internal changes by RNA editing and 30 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 30 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.
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