PMID- 36293270
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20230713
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 20
DP  - 2022 Oct 17
TI  - mTOR Contributes to the Proteome Diversity through Transcriptome-Wide Alternative 
      Splicing.
LID - 10.3390/ijms232012416 [doi]
LID - 12416
AB  - 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.
FAU - Cheng, Sze
AU  - Cheng S
AUID- ORCID: 0000-0002-0102-9812
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55445, USA.
FAU - Fahmi, Naima Ahmed
AU  - Fahmi NA
AD  - Department of Computer Science, University of Central Florida, Orlando, FL 32816, 
      USA.
FAU - Park, Meeyeon
AU  - Park M
AUID- ORCID: 0000-0001-8247-3925
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55445, USA.
FAU - Sun, Jiao
AU  - Sun J
AD  - Department of Computer Science, University of Central Florida, Orlando, FL 32816, 
      USA.
FAU - Thao, Kaitlyn
AU  - Thao K
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55445, USA.
FAU - Yeh, Hsin-Sung
AU  - Yeh HS
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55445, USA.
FAU - Zhang, Wei
AU  - Zhang W
AUID- ORCID: 0000-0003-3605-9373
AD  - Department of Computer Science, University of Central Florida, Orlando, FL 32816, 
      USA.
FAU - Yong, Jeongsik
AU  - Yong J
AUID- ORCID: 0000-0002-2758-0450
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55445, USA.
LA  - eng
GR  - R01 GM113952/GM/NIGMS NIH HHS/United States
GR  - 2R01GM113952-07/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20221017
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Proteome)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Protein Isoforms)
RN  - 0 (Untranslated Regions)
SB  - IM
MH  - *Alternative Splicing
MH  - *Transcriptome
MH  - Proteome/genetics
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Protein Isoforms/genetics
MH  - Untranslated Regions
PMC - PMC9604279
OTO - NOTNLM
OT  - alternative splicing
OT  - functional proteome
OT  - mTOR signaling
OT  - post-transcriptional gene regulation
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/29 06:00
PMCR- 2022/10/17
CRDT- 2022/10/27 01:23
PHST- 2022/08/30 00:00 [received]
PHST- 2022/09/30 00:00 [revised]
PHST- 2022/10/04 00:00 [accepted]
PHST- 2022/10/27 01:23 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/10/17 00:00 [pmc-release]
AID - ijms232012416 [pii]
AID - ijms-23-12416 [pii]
AID - 10.3390/ijms232012416 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 17;23(20):12416. doi: 10.3390/ijms232012416.