PMID- 29733382
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20240331
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 46
IP  - 12
DP  - 2018 Jul 6
TI  - An integrative model for alternative polyadenylation, IntMAP, delineates 
      mTOR-modulated endoplasmic reticulum stress response.
PG  - 5996-6008
LID - 10.1093/nar/gky340 [doi]
AB  - 3'-untranslated regions (UTRs) can vary through the use of alternative 
      polyadenylation sites during pre-mRNA processing. Multiple publically available 
      pipelines combining high profiling technologies and bioinformatics tools have 
      been developed to catalog changes in 3'-UTR lengths. In our recent RNA-seq 
      experiments using cells with hyper-activated mammalian target of rapamycin 
      (mTOR), we found that cellular mTOR activation leads to transcriptome-wide 
      alternative polyadenylation (APA), resulting in the activation of multiple 
      cellular pathways. Here, we developed a novel bioinformatics algorithm, IntMAP, 
      which integrates RNA-Seq and PolyA Site (PAS)-Seq data for a comprehensive 
      characterization of APA events. By applying IntMAP to the datasets from cells 
      with hyper-activated mTOR, we identified novel APA events that could otherwise 
      not be identified by either profiling method alone. Several transcription factors 
      including Cebpg (CCAAT/enhancer binding protein gamma) were among the newly 
      discovered APA transcripts, indicating that diverse transcriptional networks may 
      be regulated by mTOR-coordinated APA. The prevention of APA in Cebpg using the 
      CRISPR/cas9-mediated genome editing tool showed that mTOR-driven 3'-UTR 
      shortening in Cebpg is critical in protecting cells from endoplasmic reticulum 
      (ER) stress. Taken together, we present IntMAP as a new bioinformatics algorithm 
      for APA analysis by which we expand our understanding of the physiological role 
      of mTOR-coordinated APA events to ER stress response. IntMAP toolbox is available 
      at http://compbio.cs.umn.edu/IntMAP/.
FAU - Chang, Jae-Woong
AU  - Chang JW
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55455, USA.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Computer Science and Engineering, University of Minnesota Twin 
      Cities, Minneapolis, MN 55455, USA.
AD  - Department of Computer Science, University of Central Florida, Orlando, FL 32816, 
      USA.
FAU - Yeh, Hsin-Sung
AU  - Yeh HS
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55455, USA.
FAU - Park, Meeyeon
AU  - Park M
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55455, USA.
FAU - Yao, Chengguo
AU  - Yao C
AD  - Department of Microbiology and Molecular Genetics, University of California 
      School of Medicine, Irvine, CA 92697, USA.
FAU - Shi, Yongsheng
AU  - Shi Y
AD  - Department of Microbiology and Molecular Genetics, University of California 
      School of Medicine, Irvine, CA 92697, USA.
FAU - Kuang, Rui
AU  - Kuang R
AD  - Department of Computer Science and Engineering, University of Minnesota Twin 
      Cities, Minneapolis, MN 55455, USA.
FAU - Yong, Jeongsik
AU  - Yong J
AD  - Department of Biochemistry, Molecular Biology and Biophysics, University of 
      Minnesota Twin Cities, Minneapolis, MN 55455, USA.
LA  - eng
GR  - R01 GM113952/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (3' Untranslated Regions)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 136958-00-4 (Cebpg protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
MH  - 3' Untranslated Regions
MH  - *Algorithms
MH  - Animals
MH  - CCAAT-Enhancer-Binding Proteins/biosynthesis/genetics
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Stress/*genetics
MH  - Mice
MH  - *Polyadenylation
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6158760
EDAT- 2018/05/08 06:00
MHDA- 2019/07/30 06:00
PMCR- 2018/05/04
CRDT- 2018/05/08 06:00
PHST- 2017/09/20 00:00 [received]
PHST- 2018/04/20 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2018/05/04 00:00 [pmc-release]
AID - 4992652 [pii]
AID - gky340 [pii]
AID - 10.1093/nar/gky340 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2018 Jul 6;46(12):5996-6008. doi: 10.1093/nar/gky340.