title: The ever-evolving role of mTOR in translation.
abstract: 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.
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada. Electronic address: brunodfonseca@gmail.com.
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Fonseca
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: Smith
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Yelle
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada.
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bushell
authors.affiliation: Goodman Cancer Research Centre, Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: arnim.pause@mcgill.ca.
authors.forename: Arnim
authors.initials: A
authors.lastname: Pause
mesh_terms: D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics*; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012269:Ribosomal Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Protein synthesis; mRNA translation; mTOR