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题名: Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing
作者: Xiao, Wen; Adhikari, Samir; Dahal, Ujwal; Chen, Yu-Sheng; Hao, Ya-Juan; Sun, Bao-Fa; Sun, Hui-Ying; Li, Ang; Ping, Xiao-Li; Lai, Wei-Yi; Wang, Xing; Ma, Hai-Li; Huang, Chun-Min; Yang, Ying; Huang, Niu; Jiang, Gui-Bin; Wang, Hai-Lin; Zhou, Qi; Wang, Xiu-Jie; Zhao, Yong-Liang; Yang, Yun-Gui
刊名: MOLECULAR CELL
出版日期: 2016-02-18
卷号: 61, 期号:4, 页码:507-519
DOI: 10.1016/j.molcel.2016.01.012
部门归属: 环境化学与生态毒理学国家重点实验室
英文摘要: The regulatory role of N-6-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in premRNA splicing remains an enigma. Here we show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 (SRp20) while blocking SRSF10 (SRp38) mRNA binding. Transcriptome assay with PARCLIP-seq analysis revealed that YTHDC1-regulated exon-inclusion patterns were similar to those of SRSF3 but opposite of SRSF10. In vitro pull-down assay illustrated a competitive binding of SRSF3 and SRSF10 to YTHDC1. Moreover, YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 depletion, can be restored by reconstitution with wild-type, but not m(6)A-bindingdefective, YTHDC1. Our findings provide the direct evidence that m6A reader YTHDC1 regulates mRNA splicing through recruiting and modulating premRNA splicing factors for their access to the binding regions of targeted mRNAs.
收录类别: SCI
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内容类型: 期刊论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35905
Appears in Collections:环境化学与生态毒理学国家重点实验室_期刊论文

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