The core spliceosomal factor U2AF1 controls cell-fate determination via the modulation of transcriptional networks.

RNA Biology
Abdelhamid Mahdi LaarefJamal Tazi

Abstract

Alternative splicing (AS) plays a central role during cell-fate determination. However, how the core spliceosomal factors (CSFs) are involved in this process is poorly understood. Here, we report the down-regulation of the U2AF1 CSF during stem cell differentiation. To investigate its function in stemness and differentiation, we downregulated U2AF1 in human induced pluripotent stem cells (hiPSCs), using an inducible-shRNA system, to the level found in differentiated ectodermal, mesodermal and endodermal cells. RNA sequencing and computational analysis reveal that U2AF1 down-regulation modulates the expression of development-regulating genes and regulates transcriptional networks involved in cell-fate determination. Furthermore, U2AF1 down-regulation induces a switch in the AS of transcription factors (TFs) required to establish specific cell lineages, and favours the splicing of a differentiated cell-specific isoform of DNMT3B. Our results showed that the differential expression of the core spliceosomal factor U2AF1, between stem cells and the precursors of the three germ layers regulates a cell-type-specific alternative splicing programme and a transcriptional network involved in cell-fate determination via the modulation of g...Continue Reading

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Datasets Mentioned

BETA
GSM1112837

Methods Mentioned

BETA
enzymatic dissociation
RNA-seq
ChIP-seq
EISA
RNA-
seq

Software Mentioned

VastDB
STAR
TOOLS
get
MetacoreTM
VAST
MISO
MATT
STAR aligner
Cuffdiff

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