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PPR polyadenylation factor defines mitochondrial mRNA identity and stability in trypanosomes
2017-08-15
发表期刊EMBO JOURNAL (IF:9.4[JCR-2023],11.0[5-Year])
ISSN0261-4189
卷号36期号:16页码:2435-2454
发表状态已发表
DOI10.15252/embj.201796808
摘要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.
关键词pentatricopeptide repeat polyadenylation RNA editing RNA stability Trypanosoma
收录类别SCI
语种英语
资助项目NIH[AI113157] ; NIH[AI091914] ; NIH[AI101057] ; NIH[GM074830] ; NIH[GM106003]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Cell Biology
WOS记录号WOS:000407786500011
出版者WILEY
WOS关键词PENTATRICOPEPTIDE REPEAT PROTEINS ; INDUCIBLE EXPRESSION SYSTEM ; BRUCEI MITOCHONDRIA ; GUIDE RNAS ; COMPLEX ; BINDING ; TURNOVER ; RECOGNITION ; TRANSLATION ; TRANSCRIPTS
原始文献类型Article
通讯作者Aphasizheva, Inna
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/4520
专题生命科学与技术学院_PI研究组_张力烨组
通讯作者Aphasizheva, Inna
作者单位
1.Boston Univ, Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA
2.Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA
3.Univ Calif Irvine, Sch Med, Dept Physiol & Biophys, Irvine, CA 92717 USA
4.Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
第一作者单位生命科学与技术学院
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Zhang, Liye,Sement, Francois M.,Suematsu, Takuma,et al. PPR polyadenylation factor defines mitochondrial mRNA identity and stability in trypanosomes[J]. EMBO JOURNAL,2017,36(16):2435-2454.
APA Zhang, Liye.,Sement, Francois M..,Suematsu, Takuma.,Yu, Tian.,Monti, Stefano.,...&Aphasizheva, Inna.(2017).PPR polyadenylation factor defines mitochondrial mRNA identity and stability in trypanosomes.EMBO JOURNAL,36(16),2435-2454.
MLA Zhang, Liye,et al."PPR polyadenylation factor defines mitochondrial mRNA identity and stability in trypanosomes".EMBO JOURNAL 36.16(2017):2435-2454.
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