PMID- 33332560
OWN - NLM
STAT- MEDLINE
DCOM- 20210122
LR  - 20240210
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 49
IP  - 1
DP  - 2021 Jan 11
TI  - The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA 
      interaction.
PG  - 458-478
LID - 10.1093/nar/gkaa1189 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, 
      integrating multiple signalling cues and pathways. Key among the downstream 
      activities of mTOR is the control of the protein synthesis machinery. This is 
      achieved, in part, via the co-ordinated regulation of mRNAs that contain a 
      terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by 
      which this occurs downstream of mTOR signalling are still unclear. We used 
      RNA-binding protein (RBP) capture to identify changes in the protein-RNA 
      interaction landscape following mTOR inhibition. Upon mTOR inhibition, the 
      binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. 
      Importantly, non-TOP-containing mRNAs bound by LARP1 are in a 
      translationally-repressed state, even under control conditions. The mRNA 
      interactome of the LARP1-associated protein PABPC1 was found to have a high 
      degree of overlap with that of LARP1 and our data show that PABPC1 is required 
      for the association of LARP1 with its specific mRNA targets. Finally, we 
      demonstrate that mRNAs, including those encoding proteins critical for cell 
      growth and survival, are translationally repressed when bound by both LARP1 and 
      PABPC1.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Smith, Ewan M
AU  - Smith EM
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
FAU - Benbahouche, Nour El Houda
AU  - Benbahouche NEH
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
FAU - Morris, Katherine
AU  - Morris K
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Wilczynska, Ania
AU  - Wilczynska A
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
AD  - Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback 
      Road, Bearsden, Glasgow G61 1QH, UK.
FAU - Gillen, Sarah
AU  - Gillen S
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
FAU - Schmidt, Tobias
AU  - Schmidt T
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
FAU - Meijer, Hedda A
AU  - Meijer HA
AD  - Division of Cell and Developmental Biology, School of Life Sciences, University 
      of Dundee, Dundee DD1 5EH, UK.
FAU - Jukes-Jones, Rebekah
AU  - Jukes-Jones R
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Cain, Kelvin
AU  - Cain K
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Jones, Carolyn
AU  - Jones C
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Stoneley, Mark
AU  - Stoneley M
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Waldron, Joseph A
AU  - Waldron JA
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
FAU - Bell, Cameron
AU  - Bell C
AD  - Cancer Research UK Therapeutic Discovery Laboratories, London Bioscience 
      Innovation Centre, 2 Royal College Street, London NW1 0NH, UK.
FAU - Fonseca, Bruno D
AU  - Fonseca BD
AD  - PrimerGen Ltd, Viseu, Portugal.
FAU - Blagden, Sarah
AU  - Blagden S
AD  - Department of Oncology, University of Oxford, Oxford, OX3 7LE, UK.
FAU - Willis, Anne E
AU  - Willis AE
AD  - MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
FAU - Bushell, Martin
AU  - Bushell M
AD  - Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, 
      Glasgow G61 1BD, UK.
AD  - Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback 
      Road, Bearsden, Glasgow G61 1QH, UK.
LA  - eng
GR  - MC_UU_00025/6/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom
GR  - 30062/CRUK_/Cancer Research UK/United Kingdom
GR  - 22598/CRUK_/Cancer Research UK/United Kingdom
GR  - MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom
GR  - 29252/CRUK_/Cancer Research UK/United Kingdom
GR  - MC UP A600 1024/MRC_/Medical Research Council/United Kingdom
GR  - 24388/CRUK_/Cancer Research UK/United Kingdom
GR  - 1243972/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 
      (1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one)
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Autoantigens)
RN  - 0 (Naphthyridines)
RN  - 0 (Poly(A)-Binding Protein I)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - 5' Untranslated Regions/genetics
MH  - Autoantigens/genetics/*physiology
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors
MH  - Mechanistic Target of Rapamycin Complex 2/antagonists & inhibitors
MH  - Mutagenesis, Site-Directed
MH  - Mutation, Missense
MH  - Naphthyridines/pharmacology
MH  - Point Mutation
MH  - Poly(A)-Binding Protein I/*physiology
MH  - Polyribosomes/*metabolism
MH  - Protein Biosynthesis/genetics/*physiology
MH  - RNA Interference
MH  - RNA, Messenger/genetics/*metabolism
MH  - RNA-Binding Proteins/isolation & purification/metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ribonucleoproteins/genetics/*physiology
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - SS-B Antigen
PMC - PMC7797073
EDAT- 2020/12/18 06:00
MHDA- 2021/01/23 06:00
PMCR- 2020/12/17
CRDT- 2020/12/17 17:19
PHST- 2020/12/11 00:00 [accepted]
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/04/20 00:00 [received]
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/01/23 06:00 [medline]
PHST- 2020/12/17 17:19 [entrez]
PHST- 2020/12/17 00:00 [pmc-release]
AID - 6041013 [pii]
AID - gkaa1189 [pii]
AID - 10.1093/nar/gkaa1189 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2021 Jan 11;49(1):458-478. doi: 10.1093/nar/gkaa1189.