PMID- 24532714
OWN - NLM
STAT- MEDLINE
DCOM- 20140401
LR  - 20231213
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 28
IP  - 4
DP  - 2014 Feb 15
TI  - Proteomic analysis of cap-dependent translation identifies LARP1 as a key 
      regulator of 5'TOP mRNA translation.
PG  - 357-71
LID - 10.1101/gad.231407.113 [doi]
AB  - The mammalian target of rapamycin (mTOR) promotes cell growth and proliferation 
      by promoting mRNA translation and increasing the protein synthetic capacity of 
      the cell. Although mTOR globally promotes translation by regulating the mRNA 5' 
      cap-binding protein eIF4E (eukaryotic initiation factor 4E), it also 
      preferentially regulates the translation of certain classes of mRNA via unclear 
      mechanisms. To help fill this gap in knowledge, we performed a quantitative 
      proteomic screen to identify proteins that associate with the mRNA 5' cap in an 
      mTOR-dependent manner. Using this approach, we identified many potential 
      regulatory factors, including the putative RNA-binding protein LARP1 (La-related 
      protein 1). Our results indicate that LARP1 associates with actively translating 
      ribosomes via PABP and that LARP1 stimulates the translation of mRNAs containing 
      a 5' terminal oligopyrimidine (TOP) motif, encoding for components of the 
      translational machinery. We found that LARP1 associates with the mTOR complex 1 
      (mTORC1) and is required for global protein synthesis as well as cell growth and 
      proliferation. Together, these data reveal important molecular mechanisms 
      involved in TOP mRNA translation and implicate LARP1 as an important regulator of 
      cell growth and proliferation.
FAU - Tcherkezian, Joseph
AU  - Tcherkezian J
AD  - Institute for Research in Immunology and Cancer (IRIC), Universite de Montreal, 
      Montreal, Quebec H3C 3J7, Canada;
FAU - Cargnello, Marie
AU  - Cargnello M
FAU - Romeo, Yves
AU  - Romeo Y
FAU - Huttlin, Edward L
AU  - Huttlin EL
FAU - Lavoie, Genevieve
AU  - Lavoie G
FAU - Gygi, Steven P
AU  - Gygi SP
FAU - Roux, Philippe P
AU  - Roux PP
LA  - eng
GR  - R01 HG003456/HG/NHGRI NIH HHS/United States
GR  - HG3456/HG/NHGRI NIH HHS/United States
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Autoantigens)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA Cap-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleoproteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - K8CXK5Q32L (pyrimidine)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Autoantigens/genetics/*metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - *Proteomics
MH  - Pyrimidines/*metabolism
MH  - RNA Cap-Binding Proteins/metabolism
MH  - RNA, Messenger/*genetics
MH  - Ribonucleoproteins/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - SS-B Antigen
PMC - PMC3937514
OTO - NOTNLM
OT  - 5'TOP
OT  - LARP1
OT  - mRNA
OT  - mTOR
OT  - proteomics
OT  - translation
EDAT- 2014/02/18 06:00
MHDA- 2014/04/02 06:00
PMCR- 2014/08/15
CRDT- 2014/02/18 06:00
PHST- 2014/02/18 06:00 [entrez]
PHST- 2014/02/18 06:00 [pubmed]
PHST- 2014/04/02 06:00 [medline]
PHST- 2014/08/15 00:00 [pmc-release]
AID - 28/4/357 [pii]
AID - 10.1101/gad.231407.113 [doi]
PST - ppublish
SO  - Genes Dev. 2014 Feb 15;28(4):357-71. doi: 10.1101/gad.231407.113.