February 18, 2016 | Wen Xiao, Samir Adhikari, Ujwal Dahal, ..., Xiu-Jie Wang, Yong-Liang Zhao, Yun-Gui Yang
The study by Xiao et al. investigates the role of the N6-methyladenosine (m6A) reader YTHDC1 in mRNA splicing. They find that YTHDC1 promotes exon inclusion in targeted mRNAs by recruiting the pre-mRNA splicing factor SRSF3 while blocking the binding of SRSF10 to mRNAs. Transcriptome analysis and PAR-CLIP-seq revealed that YTHDC1-regulated exon-inclusion patterns are similar to those of SRSF3 but opposite to those of SRSF10. In vitro pull-down assays confirmed the competitive binding of SRSF3 and SRSF10 to YTHDC1. YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events. The findings provide direct evidence that m6A reader YTHDC1 regulates mRNA splicing by recruiting and modulating pre-mRNA splicing factors to their target mRNAs.The study by Xiao et al. investigates the role of the N6-methyladenosine (m6A) reader YTHDC1 in mRNA splicing. They find that YTHDC1 promotes exon inclusion in targeted mRNAs by recruiting the pre-mRNA splicing factor SRSF3 while blocking the binding of SRSF10 to mRNAs. Transcriptome analysis and PAR-CLIP-seq revealed that YTHDC1-regulated exon-inclusion patterns are similar to those of SRSF3 but opposite to those of SRSF10. In vitro pull-down assays confirmed the competitive binding of SRSF3 and SRSF10 to YTHDC1. YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events. The findings provide direct evidence that m6A reader YTHDC1 regulates mRNA splicing by recruiting and modulating pre-mRNA splicing factors to their target mRNAs.