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

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 gene expression and alternative splicing of transcription regulators.

journal_name

RNA Biol

journal_title

RNA biology

authors

Laaref AM,Manchon L,Bareche Y,Lapasset L,Tazi J

doi

10.1080/15476286.2020.1733800

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

857-871

issue

6

eissn

1547-6286

issn

1555-8584

journal_volume

17

pub_type

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