Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors.

Liu, R, Iadevaia, V, Averous, J, Taylor, PM, Zhang, Z and Proud, CG (2014) Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors. Nucleic Acids Res, 42 (8). pp. 5083-5096.

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Abstract

Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all these processes. Here, we show that, in human cells, impaired rRNA processing, caused by expressing an interfering mutant of BOP1 or by knocking down components of the PeBoW complex elicits activation of mTORC1 signalling. This leads to enhanced phosphorylation of its substrates S6K1 and 4E-BP1, and stimulation of proteins involved in translation initiation and elongation. In particular, we observe both inactivation and downregulation of the eukaryotic elongation factor 2 kinase, which normally inhibits translation elongation. The latter effect involves decreased expression of the eEF2K mRNA. The mRNAs for ribosomal proteins, whose translation is positively regulated by mTORC1 signalling, also remain associated with ribosomes. Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production.

Item Type:	Article
Divisions :	Surrey research (other units)
Authors :	Name Email ORCID Liu, R Iadevaia, V v.iadevaia@surrey.ac.uk Averous, J Taylor, PM Zhang, Z Proud, CG
Date :	April 2014
DOI :	10.1093/nar/gku130
Uncontrolled Keywords :	Cell Line, Elongation Factor 2 Kinase, Eukaryotic Initiation Factors, Humans, Multiprotein Complexes, Peptide Elongation Factor 2, Peptide Elongation Factors, Phosphorylation, Polyribosomes, Protein Biosynthesis, Proteins, RNA, Ribosomal, Ribosomal Protein S6 Kinases, Sequence Deletion, Signal Transduction, TOR Serine-Threonine Kinases
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 10:28
Last Modified :	24 Jan 2020 19:23
URI:	http://epubs.surrey.ac.uk/id/eprint/827933

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