2013
DOI: 10.1038/nature12270
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MBNL proteins repress ES-cell-specific alternative splicing and reprogramming

Abstract: Previous investigations of the core gene regulatory circuitry that controls embryonic stem cell (ESC) pluripotency have largely focused on the roles of transcription, chromatin and non-coding RNA regulators1–3. Alternative splicing (AS) represents a widely acting mode of gene regulation4–8, yet its role in regulating ESC pluripotency and differentiation is poorly understood. Here, we identify the Muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large prog… Show more

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Cited by 290 publications
(375 citation statements)
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“…We also provide insight into the regulation of CnA post-transcriptional processing that leads to expression of CnAβ1. We show for the first time that CnA splicing is controlled, at least in part, by Mbnl1, which has a similar role to that of CnAβ1 in the differentiation of ESCs (Han et al, 2013). Mbnl1 was previously shown to favor ESC differentiation by controlling AS of different genes.…”
Section: Discussionmentioning
confidence: 56%
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“…We also provide insight into the regulation of CnA post-transcriptional processing that leads to expression of CnAβ1. We show for the first time that CnA splicing is controlled, at least in part, by Mbnl1, which has a similar role to that of CnAβ1 in the differentiation of ESCs (Han et al, 2013). Mbnl1 was previously shown to favor ESC differentiation by controlling AS of different genes.…”
Section: Discussionmentioning
confidence: 56%
“…2SA and B). It has been recently described that muscleblind like (Mbnl) proteins are major splicing regulators in ESCs that repress pluripotency and promote differentiation (Han et al, 2013). To investigate the potential regulation of CnA splicing by Mbnl1, we first explored available CLIP-Seq datasets for this trans-regulatory factor obtained from myoblasts and differentiated tissues (Wang et al, 2012).…”
Section: Cnaβ1 Is Necessary For Mesoderm Differentiationmentioning
confidence: 99%
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“…RBPs play a crucial role in regulating splicing, having an impact on a wide variety of developmental stages such as stem cell differentiation 46 and tissue development 47 . We predicted binding scores at junctions near exons that are putatively regulated by known splicing regulators that exhibit large changes in splicing when knocked down, including: Nova (neuro-oncological ventral antigen 1 and 2), PTBP1 (polypyrimidine tract binding protein 1), Mbnl1/2 (muscleblind-like protein), hnRNP C (heterogeneous nuclear ribonucleoprotein C) and cytotoxic TIA (T-cell intracellular antigen-like 1).…”
Section: Deepbind Models Identify Deleterious Genomic Variantsmentioning
confidence: 99%