Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing

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	Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing
	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
刊名	MOLECULAR CELL
	2016-02-18
卷号	61 期号:4 页码:507-519
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
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/35905]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Xiao, Wen,Adhikari, Samir,Dahal, Ujwal,et al. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing[J]. MOLECULAR CELL,2016,61(4):507-519.
APA	Xiao, Wen.,Adhikari, Samir.,Dahal, Ujwal.,Chen, Yu-Sheng.,Hao, Ya-Juan.,...&Yang, Yun-Gui.(2016).Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.MOLECULAR CELL,61(4),507-519.
MLA	Xiao, Wen,et al."Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing".MOLECULAR CELL 61.4(2016):507-519.