Nuclear m6A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3′ processing machinery

被引：24

作者：

Chen, Liutao ^{[1
]}

Fu, Yonggui ^{[1
]}

Hu, Zhijie ^{[1
]}

Deng, Ke ^{[1
]}

Song, Zili ^{[1
]}

Liu, Susu ^{[1
]}

Li, Mengxia ^{[1
]}

Ou, Xin ^{[1
]}

Wu, Runze ^{[1
]}

Liu, Mian ^{[1
]}

Li, Rui ^{[1
]}

Gao, Shuiying ^{[1
]}

Cheng, Lin ^{[1
]}

Chen, Shangwu ^{[1
]}

Xu, Anlong ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ, Sch Life Sci, Higher Educ Mega Ctr, Dept Biochem,State Key Lab Biocontrol,Guangdong P, Guangzhou, Peoples R China

[2] Beijing Univ Chinese Med, Sch Life Sci, Beijing, Peoples R China

来源：

EMBO REPORTS | 2022年 / 23卷 / 11期

基金：

中国国家自然科学基金;

关键词：

3 ' end processing factor; alternative polyadenylation; FIP1L1; m(6)A; YTHDC1; DYNAMIC RNA MODIFICATIONS; STRUCTURAL BASIS; MESSENGER-RNAS; METHYLATION; N6-METHYLADENOSINE; UTRS; TRANSCRIPTION; TRANSLATION; ENRICHMENT; REVEALS;

D O I：

10.15252/embr.202254686

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N6-methyladenosine (m(6)A) and alternative polyadenylation (APA) are important regulators of gene expression in eukaryotes. Recently, it was found that m(6)A is closely related to APA. However, the molecular mechanism of this new APA regulation remains elusive. Here, we show that YTHDC1, a nuclear m(6)A reader, can suppress proximal APA sites and produce longer 3' UTR transcripts by binding to their upstream m(6)A sites. YTHDC1 can directly interact with the 3' end processing factor FIP1L1 and interfere with its ability to recruit CPSF4. Binding to the m(6)A sites can promote liquid- liquid phase separation of YTHDC1 and FIP1L1, which may play an important role in their interaction and APA regulation. Collectively, YTHDC1 as an m(6)A "reader" links m(6)A modification with pre-mRNA 3' end processing, providing a new mechanism for APA regulation.

引用

页数：18

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