Alternative splicing regulation of membrane trafficking genes during myogenesis

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...

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Published inRNA (Cambridge) Vol. 28; no. 4; pp. 523 - 540
Main Authors Hinkle, Emma R, Wiedner, Hannah J, Torres, Eduardo V, Jackson, Micaela, Black, Adam J, Blue, R Eric, Harris, Sarah E, Guzman, Bryan B, Gentile, Gabrielle M, Lee, Eunice Y, Tsai, Yi-Hsuan, Parker, Joel, Dominguez, Daniel, Giudice, Jimena
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.04.2022
Subjects
Alternative Splicing
Animals
Cell differentiation
Chromatin
Exons
Fetuses
Gene regulation
Heterogeneous-Nuclear Ribonucleoproteins - genetics
Heterogeneous-Nuclear Ribonucleoproteins - metabolism
Membrane trafficking
Mice
Muscle Development - genetics
Muscles
Myogenesis
Polypyrimidine Tract-Binding Protein - genetics
Polypyrimidine Tract-Binding Protein - metabolism
Proteins
RNA-binding protein
RNA-binding proteins
alternative splicing
myogenesis
membrane trafficking
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Summary: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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These authors contributed equally to this work.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.078993.121