Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors
Author: Liu, R.
Iadevaia, V.
Averous, J.
Taylor, P.
Zhang, Z.
Proud, C.
Citation: Nucleic Acids Research, 2014; 42(8):5083-5096
Publisher: Oxford University Press
Issue Date: 2014
ISSN: 0305-1048
Statement of
Rui Liu, Valentina Iadevaia, Julien Averous, Peter M. Taylor, Ze Zhang and Christopher G. Proud
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.
Keywords: Cell Line
Rights: © The Author(s) 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0030035735
DOI: 10.1093/nar/gku130
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
File Description SizeFormat 
hdl_97654.pdfPublished version3.77 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.