期刊
CELL REPORTS
卷 7, 期 6, 页码 1900-1913出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.05.010
关键词
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类别
资金
- INSERM
- INCa
- Fondation pour la Recherche Medicale (FRM)
- LNCC
- AFM-Telethon
- AFM
- French Ministere de l'Enseignement Superieur et de la Recherche
- FRM
- Centre Leon Berard
- Fondation ARC
The RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins that are involved in gene-expression regulation; however, their in vivo targets and activities in biological processes such as cell differentiation, which requires reprogramming of gene-expression programs at multiple levels, are not well characterized. Here, we uncovered a mechanism by which DDX5 and DDX17 cooperate with heterogeneous nuclear ribonucleoprotein (hnRNP) H/F splicing factors to define epithelial-and myoblast-specific splicing subprograms. We then observed that downregulation of DDX5 and DDX17 protein expression during myogenesis and epithelial-to-mesenchymal transdifferentiation contributes to the switching of splicing programs during these processes. Remarkably, this downregulation is mediated by the production of miRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation that dynamically orchestrate several layers of gene expression.
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