Alternative Splicing of Neuronal Differentiation Factor TRF2 Regulated by HNRNPH1/H2

• DOI: 10.1016/j.celrep.2016.03.080
• Publication Date: 2016-04-30T18:48:37Z
• Authors: Ioannis Grammatik...; Peisu Zhang; Amaresh C. Panda; Jiyoung Kim; Stuart Maudsley; Kotb Abdelmohsen; Xiaoling Yang; Jennifer L. Marti...; Omar Motiño; Emmette R. Hutchison; Mark P. Mattson; Myriam Gorospe
• Keywords: Splicing factor

Highlights•A splice variant of TRF2 with a short exon 7 (TRF2-S) arises during neurogenesis•HNRNPH1/H2 binds Trf2 and represses splicing into TRF2-S•During neurogenesis, HNRNPH1/H2 levels decline while TRF2-S increase•Silencing elevates promotes neurogenesisSummaryDuring neuronal differentiation, use an alternative site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates protein isoform capable derepressing genes. However, RNA-binding proteins (RBPs) controlling this event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 H2(HNRNPH) as RBPs specifically interacting spliced RNA segment (exon 7) pre-mRNA. HNRNPH prevent production mRNA, silencing selectively levels. Accordingly, increase differentiation. In addition, CRISPR/Cas9-mediated deletion hnRNPH2 accelerates NGF-triggered differentiation pheochromocytoma cells neurons. sum, is regulator pre-mRNA that prevents expression TRF2-S, implicated in differentiation.Graphical abstract