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Title
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Alternative splicing of neuronal differentiation factor TRF2 regulated by HNRNPH1/H2
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Author
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Abstract
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| During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. Accordingly, HNRNPH levels decline while TRF2-S levels increase during neuronal differentiation. In addition, CRISPR/Cas9-mediated deletion of hnRNPH2 selectively accelerates the NGF-triggered differentiation of rat pheochromocytoma cells into neurons. In sum, HNRNPH is a splicing regulator of Trf2 pre-mRNA that prevents the expression of TRF2-S, a factor implicated in neuronal differentiation. |
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Language
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English
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Source (journal)
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Cell reports
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Publication
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2016
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ISSN
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2211-1247
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DOI
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10.1016/J.CELREP.2016.03.080
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Volume/pages
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15
:5
(2016)
, p. 926-934
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ISI
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000376164600003
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Pubmed ID
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27117401
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Full text (Publisher's DOI)
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Full text (open access)
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