4.6 Review

The ever-evolving role of mTOR in translation

Journal

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 36, Issue -, Pages 102-112

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2014.09.014

Keywords

mRNA translation; Protein synthesis; mTOR

Funding

  1. U.S. Department of Defense Prostate Cancer Research Fellow Grant Award [PC093125]
  2. Children's Hospital of Eastern Ontario (CHEO) Foundation [9960]
  3. Kidney Foundation of Canada
  4. Terry Fox Research Institute
  5. Cancer Research Society
  6. Canadian Cancer Society Research Institute
  7. BBSRC [BB/F011806/2, BB/F019017/1, BB/F011806/1, BB/F019017/2] Funding Source: UKRI
  8. MRC [MC_EX_G0902052, MC_UP_A600_1024] Funding Source: UKRI
  9. Biotechnology and Biological Sciences Research Council [BB/F019017/2, BB/F011806/2, BB/C516095/1, BB/F019017/1, BB/F011806/1, BB/B500915/1] Funding Source: researchfish
  10. Medical Research Council [MC_EX_G0902052, MC_UP_A600_1024] Funding Source: researchfish

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Control of translation allows for the production of stoichiometric levels of each protein in the cell. Attaining such a level of fine-tuned regulation of protein production requires the coordinated temporal and spatial control of numerous cellular signalling cascades impinging on the various components of the translational machinery. Foremost among these is the mTOR signalling pathway. The mTOR pathway regulates both the initiation and elongation steps of protein synthesis through the phosphorylation of numerous translation factors, while simultaneously ensuring adequate folding of nascent polypeptides through co-translational degradation of misfolded proteins. Perhaps most remarkably, mTOR is also a key regulator of the synthesis of ribosomal proteins and translation factors themselves. Two seminal studies have recently shown in translatome analysis that the mTOR pathway preferentially regulates the translation of mRNAs encoding ribosomal proteins and translation factors. Therefore, the role of the mTOR pathway in the control of protein synthesis extends far beyond immediate translational control. By controlling ribosome production (and ultimately ribosome availability), mTOR is a master long-term controller of protein synthesis. Herein, we review the literature spanning the early discoveries of mTOR on translation to the latest advances in our understanding of how the mTOR pathway controls the synthesis of ribosomal proteins. Crown Copyright (C) 2014 Published by Elsevier Ltd. All rights reserved.

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