The mammalian target of rapamycin (mTOR) pathway is crucial in energy metabolism and 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: 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.
Bibliographical noteFunding Information:
This work was supported by National Science Foundation [NSF-III1755761] to W.Z. and National Institutes of Health [2R01GM113952] and Department of Defense—Congressionally Directed Medical Research Programs [W81XWH-16-1-0135] to J.Y. S.C. was supported by the ARCS Foundation.
© 2022 by the authors.
- alternative splicing
- functional proteome
- mTOR signaling
- post-transcriptional gene regulation
PubMed: MeSH publication types
- Journal Article