The impact of Hnrnpl deficiency on transcriptional patterns of developing muscle cells

Le résumé fourni par la source

Heterogeneous nuclear ribonucleoproteins (hnRNPs) bind to RNA, regulating gene expression and splicing. HnRNP L contributes to muscle development and the pathogenesis of myotonic dystrophy. We hypothesized that hnRNP L regulates muscle expression and splicing patterns. Using nanopore long-read transcriptome sequencing and qPCR analyses, we investigated the impact of Hnrnpl knockdown on myoblasts and knockdown of the orthologous gene smooth in Drosophila. Notch signaling genes and muscle-related genes were dysregulated in both models. Several genes had altered splicing patterns, including Lamp2, Fhl1, and Dtna. The α-DB1 isoform of Dtna was downregulated, whereas the α-DB3 isoform was upregulated. Our findings indicate that hnRNP L regulates both the transcription levels and splicing patterns of genes relevant to skeletal muscle development. We demonstrate the capabilities of long-read transcriptome sequencing to study muscle development. Comparisons between nanopore long-read transcriptome sequencing and data from PCR and qPCR analyses suggest that a minimum read depth of 10 is needed on nanopore sequencing to detect splicing differences greater than 10% to 20%. Future studies could determine whether the minimum read depth that we identified in our model is valid across a broader range of genes, cell types, and conditions. There are also intriguing hints of therapeutic implications of hnRNP L regulation for muscle diseases that merit further investigation.

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