期刊
RNA
卷 28, 期 4, 页码 523-540出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.078993.121
关键词
alternative splicing; myogenesis; RNA-binding proteins; membrane trafficking
资金
- Jefferson Pilot Award
- University of North Carolina at Chapel Hill
- National Institutes of Health [NIH-NIGMS R01GM130866]
- American Heart Association [19CDA34660248]
- NIH-NIAMS F31 predoctoral fellowship [AR077381-01A1]
- NIH-NIGMS training award [T32GM008570]
- Graduate School at The University of North Carolina at Chapel Hill [T32GM119999]
- NSF Graduate Research Fellowship Program [DGE-1650116]
- Chancellor's Science Scholars Program at the University ofNorth Carolina at Chapel Hill
- NIH-NHLBI F32 postdoctoral fellowship [F32HL149147]
- NIH-NIGMS [T32GM135095, R25GM055336]
- Genetics and Molecular Biology Curriculum (GMB)
- Program in Translational Medicine
- Mechanistic and Interdisciplinary Biology (MiBio) Graduate Training Program
This study found that alternative splicing programs play an important role in organ development and diseases. Extensive splicing changes occur in genes related to vesicle-mediated trafficking during postnatal mouse heart development. PTBP1 and quaking were identified as regulators of splicing in muscle cells.
Alternative splicing transitions occur during organ development, and, in numerous diseases, splicing programs revert to fetal isoform expression. We previously found that extensive splicing changes occur during postnatal mouse heart development in genes encoding proteins involved in vesicle-mediated trafficking. However, the regulatory mechanisms of this splicing-trafficking network are unknown. Here, we found that membrane trafficking genes are alternatively spliced in a tissue-specific manner, with striated muscles exhibiting the highest levels of alternative exon inclusion. Treatment of differentiated muscle cells with chromatin-modifying drugs altered exon inclusion in muscle cells. Examination of several RNA-binding proteins revealed that the poly-pyrimidine tract binding protein 1 (PTBP1) and quaking regulate splicing of trafficking genes during myogenesis, and that removal of PTBP1 motifs prevented PTBP1 from binding its RNA target. These findings enhance our understanding of developmental splicing regulation of membrane trafficking proteins which might have implications for muscle disease pathogenesis.
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