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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Liu R,Iadevaia V,Averous J,Taylor PM,Zhang Z,Proud CG

doi

10.1093/nar/gku130

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

5083-96

issue

8

eissn

0305-1048

issn

1362-4962

pii

gku130

journal_volume

42

pub_type

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