mTOR Contributes to the Proteome Diversity through Transcriptome-Wide Alternative Splicing

Sze Cheng, Naima Ahmed Fahmi, Meeyeon Park, Jiao Sun, Kaitlyn Thao, Hsin Sung Yeh, Wei Zhang, Jeongsik Yong

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number12416
JournalInternational journal of molecular sciences
Issue number20
StatePublished - Oct 2022

Bibliographical note

Funding 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.

Publisher Copyright:
© 2022 by the authors.


  • alternative splicing
  • functional proteome
  • mTOR signaling
  • post-transcriptional gene regulation

PubMed: MeSH publication types

  • Journal Article


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