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bioRxiv · 10.1101/2020.02.27.967737

mTOR-driven widespread exon skipping renders multifaceted gene regulation and proteome complexity

Cheng, S.·Fahmi, N. A.·Park, M.·Chang, J.-W.·Sun, J.·Thao, K.·Yeh, H.-S.·Zhang, W.·Yong, J.
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Abstract

The mammalian target of rapamycin (mTOR) pathway is crucial in cell proliferation. Previously, we reported transcriptome-wide 3’-untranslated region (UTR) shortening by alternative polyadenylation upon mTOR activation and its impact on the proteome. Here, we further interrogated the mTOR-activated transcriptome and found that hyperactivation of mTOR promotes transcriptome-wide exon-skipping/exclusion, producing short isoform transcripts from genes. This widespread exon skipping confers multifarious regulations in the mTOR-controlled functional proteomics: alternative splicing (AS) in the 5’-UTR controls translation efficiency while AS in coding regions widely affects the protein length and functional domains. They also alter the half-life of proteins and affect the regulatory post-translational modifications. Among the RNA processing factors differentially regulated by mTOR signaling, we found that SRSF3 mechanistically facilitates exon skipping in the mTOR-activated transcriptome. This study reveals a role of mTOR in AS regulation and demonstrates that widespread AS is a multifaceted modulator of the mTOR-regulated functional proteome.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Cheng, S., Fahmi, N. A., Park, M., Chang, J.-W., Sun, J., Thao, K., Yeh, H.-S., Zhang, W., Yong, J.. 2020-02-27. mTOR-driven widespread exon skipping renders multifaceted gene regulation and proteome complexity. https://doi.org/10.1101/2020.02.27.967737

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