mTOR Contributes to the Proteome Diversity through Transcriptome-Wide Alternative Splicing
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 17, 2022
- Source ID
- 10.3390/ijms232012416
Entities
People
- Hsin-sung Yeh
- Jeongsik Yong
- Jiao Sun
- Kaitlyn Thao
- Mee Yeon Park
- Naima Ahmed Fahmi
- Sze Cheng
- Wei Zhang
Organizations
- National Institute of General Medical Sciences
- National Science Foundation
- United States Department of Defense