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The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

  • Smith, Ewan M1
  • Benbahouche, Nour El Houda1
  • Morris, Katherine2
  • Wilczynska, Ania1, 3
  • Gillen, Sarah1
  • Schmidt, Tobias1
  • Meijer, Hedda A4
  • Jukes-Jones, Rebekah2
  • Cain, Kelvin2
  • Jones, Carolyn2
  • Stoneley, Mark2
  • Waldron, Joseph A1
  • Bell, Cameron5
  • Fonseca, Bruno D6
  • Blagden, Sarah7
  • Willis, Anne E2
  • Bushell, Martin1, 3
  • 1 Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
  • 2 MRC Toxicology Unit, University of Cambridge, Leicester LE1 9HN, UK.
  • 3 Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK.
  • 4 Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
  • 5 Cancer Research UK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK.
  • 6 PrimerGen Ltd, Viseu, Portugal. , (Portugal)
  • 7 Department of Oncology, University of Oxford, Oxford, OX3 7LE, UK.
Published Article
Nucleic Acids Research
Oxford University Press
Publication Date
Jan 11, 2021
DOI: 10.1093/nar/gkaa1189
PMID: 33332560


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. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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