Nuclear m6A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3′ processing machinery
Nuclear m6A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3′ processing machinery
复制标题
核 m 6 A 阅读器 YTHDC1 通过干扰 3 加工机制来抑制近端选择性多聚腺苷酸化位点
DOI：
10.15252/embr.202254686
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发表时间：
2022-09-12
期刊：
影响因子：
7.7
通讯作者：
Xu, Anlong
中科院分区：
文献类型：
--
作者：
Chen, Liutao;Fu, Yonggui;Xu, Anlong
N6-甲基腺苷（m（6）A）和交替多聚腺苷酸化（APA）是真核生物基因表达的重要调控因子。最近发现m（6）A与APA密切相关。然而，这种新的APA调节的分子机制仍然难以捉摸。在这里，我们发现YTHDC1，一个核m（6）A阅读器，可以抑制近端APA位点，并通过结合上游m（6）A位点产生更长的3 'UTR转录本。YTHDC1可以直接与3 '端加工因子FIP1L1相互作用，并干扰其募集CPSF 4的能力。与m（6）A位点结合可促进YTHDC1和FIP1L1的液-液相分离，这可能在它们的相互作用和APA调节中起重要作用。总的来说，YTHDC1作为m（6）A "阅读器"将m（6）A修饰与前体mRNA 3 '端加工联系起来，为APA调节提供了新的机制。
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.