Article

Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis.

School of Biological Sciences, Life Sciences Building, Highfield Campus, University of Southampton, Southampton SO17 1BJ, UK.
Biochemical Society Transactions (impact factor: 3.71). 02/2012; 40(1):168-72. DOI:10.1042/BST20110682 pp.168-72
Source: PubMed

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.

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    PLoS Genetics 03/2013; 9(3):e1003389. · 8.69 Impact Factor
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    [show abstract] [hide abstract]
    ABSTRACT: [This corrects the article on p. e1003389 in vol. 9.].
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Keywords

5'-terminal pyrimidine tract
 
anabolic metabolism
 
cell growth
 
cellular energy status
 
diverse signals
 
greater inhibition
 
growth factors
 
human cells
 
inhibiting mTOR kinase activity causes
 
limited impact
 
mammalian target
 
mRNAs encode ribosomal proteins
 
mTOR kinase inhibitors
 
Partial inhibition
 
protein synthesis
 
proteins encoded
 
pulsed stable-isotope-labelling technique
 
rapamycin complex 1
 
ribosome biogenesis
 
specific proteins