Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei

doi:10.1093/nar/gkaa575

	Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei
	Aphasizheva, Inna 1; Yu, Tian 1; Suematsu, Takuma 1; Liu, Qiushi 1; Mesitov, Mikhail, V 1; Yu, Clinton 2; Huang, Lan 2; Zhang, Liye3 ; Aphasizhev, Ruslan 1,4
	2020-09-04
发表期刊	NUCLEIC ACIDS RESEARCH (IF:16.6[JCR-2023],16.1[5-Year])
ISSN	0305-1048
卷号	48 期号:15 页码:8645-8662
DOI	10.1093/nar/gkaa575
摘要	In Trypanosoma brucei, mitochondrial pre-mRNAs undergo 3'-5' exonucleolytic processing, 3' adenylation and uridylation, 5' pyrophosphate removal, and, often, U-insertion/deletion editing. The 3' modifications are modulated by pentatricopeptide repeat (PPR) Kinetoplast Polyadenylation Factors (KPAFs). We have shown that KPAF3 binding to the 3' region stabilizes properly trimmed transcripts and stimulates their A-tailing by KPAP1 poly(A) polymerase. Conversely, poly(A) binding KPAF4 shields the nascent A-tail from uridylation and decay thereby protecting pre-mRNA upon KPAF3 displacement by editing. While editing concludes in the 5' region, KPAF1/2 dimer induces A/U-tailing to activate translation. Remarkably, 5' end recognition and pyrophosphate hydrolysis by the PPsome complex also contribute to mRNA stabilization. Here, we demonstrate that KPAF4 functions as a heterodimer with KPAF5, a protein lacking discernable motifs. We show that KPAF5 stabilizes KPAF4 to enable poly(A) tail recognition, which likely leads to mRNA stabilization during the editing process and impedes spontaneous translational activation of partially-edited transcripts. Thus, KPAF4/5 represents a poly(A) binding element of the mitochondrial polyadenylation complex. We present evidence that RNA editing substrate binding complex bridges the 5' end-bound PPsome and 3' end-bound polyadenylation complexes. This interaction may enable mRNA circularization, an apparently critical element of mitochondrial mRNA stability and quality control.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Institutes of Health[AI091914][AI101057 09][AI113157][GM130144]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000574315100036
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123579
专题	生命科学与技术学院_PI研究组_张力烨组
通讯作者	Aphasizhev, Ruslan
作者单位	1.Boston Univ, Dept Mol & Cell Biol, Med Campus, Boston, MA 02118 USA; 2.Univ Calif Irvine, Sch Med, Dept Physiol & Biophys, Irvine, CA 92697 USA; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 4.Boston Univ, Dept Biochem, Med Campus, Boston, MA 02118 USA
推荐引用方式 GB/T 7714	Aphasizheva, Inna,Yu, Tian,Suematsu, Takuma,et al. Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei[J]. NUCLEIC ACIDS RESEARCH,2020,48(15):8645-8662.
APA	Aphasizheva, Inna.,Yu, Tian.,Suematsu, Takuma.,Liu, Qiushi.,Mesitov, Mikhail, V.,...&Aphasizhev, Ruslan.(2020).Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei.NUCLEIC ACIDS RESEARCH,48(15),8645-8662.
MLA	Aphasizheva, Inna,et al."Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei".NUCLEIC ACIDS RESEARCH 48.15(2020):8645-8662.