Alternative splicing regulation of membrane trafficking genes during myogenesis
| Autor: | Emma R. Hinkle, Hannah J. Wiedner, Eduardo V. Torres, Micaela Jackson, Adam J. Black, R. Eric Blue, Sarah E. Harris, Bryan B. Guzman, Gabrielle M. Gentile, Eunice Y. Lee, Yi-Hsuan Tsai, Joel Parker, Daniel Dominguez, Jimena Giudice |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | RNA. 28:523-540 |
| ISSN: | 1469-9001 1355-8382 |
| DOI: | 10.1261/rna.078993.121 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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