m6A reader YTHDC1 regulates mRNA splicing

来源 :2015 Genomics Frontiers Symposium(2015基因组学前沿研讨会) | 被引量 : 0次 | 上传用户:1liuxiewei2
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  The regulatory role of N6-methyladenosine (m6A) and its nuclear reader 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 C1BP3 while blocking C1BP10 binding.Transcriptome assay with PAR-CLIP-Seq analysis revealed that YTHDC 1-regulated exon-inclusion patterns were similar as C1BP3 but opposite to C1BP10.In vitro pull-down assay illustrated a competitive binding of C-terminus RS domain of C1BP3 or C1BP10 to YTHDC1.Moreover,YTHDC1 facilitates C1BP3 but represses C1BP10 in their nuclear speckle localization, RNA binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 knock-down, can be restored by reconstitution with wild-type but not m6A binding-defective YTHDC1.Our findings provide the direct evidence that m6A reader YTHDC1 controls mRNA splicing of target genes through recruiting and modulating pre-mRNA splicing factors for their access to the binding motifs of mRNAs.
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