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. 2016 Feb 18;61(4):507-519.
doi: 10.1016/j.molcel.2016.01.012. Epub 2016 Feb 11.

V体育2025版 - Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing

Wen Xiao  1 , Samir Adhikari  1 , Ujwal Dahal  1 , Yu-Sheng Chen  1 , Ya-Juan Hao  1 , Bao-Fa Sun  2 , Hui-Ying Sun  1 , Ang Li  1 , Xiao-Li Ping  3 , Wei-Yi Lai  4 , Xing Wang  1 , Hai-Li Ma  1 , Chun-Min Huang  3 , Ying Yang  3 , Niu Huang  5 , Gui-Bin Jiang  4 , Hai-Lin Wang  4 , Qi Zhou  6 , Xiu-Jie Wang  7 , Yong-Liang Zhao  8 , Yun-Gui Yang  9
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Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing

Wen Xiao et al. Mol Cell. .
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Erratum in

  • Mol Cell. 2016 Mar 17;61(6):925

V体育2025版 - Abstract

The regulatory role of N(6)-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in pre-mRNA 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 PAR-CLIP-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-binding-defective, YTHDC1. Our findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs. VSports手机版.

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