title: Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis.
abstract: mTORC1 (mammalian target of rapamycin complex 1) is controlled by diverse signals (e.g. hormones, growth factors, nutrients and cellular energy status) and regulates a range of processes including anabolic metabolism, cell growth and cell division. We have studied the impact of inhibiting mTOR on protein synthesis in human cells. Partial inhibition of mTORC1 by rapamycin has only a limited impact on protein synthesis, but inhibiting mTOR kinase activity causes much greater inhibition of protein synthesis. Using a pulsed stable-isotope-labelling technique, we show that the rapamycin and mTOR (mammalian target of rapamycin) kinase inhibitors have differential effects on the synthesis of specific proteins. In particular, the synthesis of proteins encoded by mRNAs that have a 5'-terminal pyrimidine tract is strongly inhibited by mTOR kinase inhibitors. Many of these mRNAs encode ribosomal proteins. mTORC1 also promotes the synthesis of rRNA, although the mechanisms involved remain to be clarified. We found that mTORC1 also regulates the processing of the precursors of rRNA. mTORC1 thus co-ordinates several steps in ribosome biogenesis.
authors.affiliation: School of Biological Sciences, Life Sciences Building, Highfield Campus, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iadevaia
authors.forename: Yilin
authors.initials: Y
authors.lastname: Huo
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhang
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C493245:CRTC2 protein, human; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus