Functional interplay between E2F7 and ribosomal rRNA gene transcription regulates protein synthesis

Coutts, AS ORCID: https://orcid.org/0000-0002-5005-1864, Munro, S and La Thangue, NB, 2018. Functional interplay between E2F7 and ribosomal rRNA gene transcription regulates protein synthesis. Cell Death & Disease, 9: 577. ISSN 2041-4889

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Abstract

A prerequisite for protein synthesis is the transcription of ribosomal rRNA genes by RNA polymerase I (Pol I), which controls ribosome biogenesis. UBF (upstream binding factor) is one of the main Pol I transcription factors located in the nucleolus that activates rRNA gene transcription. E2F7 is an atypical E2F family member that acts as a transcriptional repressor of E2F target genes, and thereby contributes to cell cycle arrest. Here, we describe an unexpected role for E2F7 in regulating rRNA gene transcription. We have found that E2F7 localises to the perinucleolar region, and further that E2F7 is able to exert repressive effects on Pol I transcription. At the mechanistic level, this is achieved in part by E2F7 hindering UBF recruitment to the rRNA gene promoter region, and thereby reducing rRNA gene transcription, which in turn compromises global protein synthesis. Our results expand the target gene repertoire influenced by E2F7 to include Pol I-regulated genes, and more generally suggest a mechanism mediated by effects on Pol I transcription where E2F7 links cell cycle arrest with protein synthesis.

Item Type:	Journal article
Publication Title:	Cell Death & Disease
Creators:	Coutts, A.S., Munro, S. and La Thangue, N.B.
Publisher:	Nature Publishing Group
Date:	14 May 2018
Volume:	9
ISSN:	2041-4889
Identifiers:	Number Type 10.1038/s41419-018-0529-6 DOI 529 Publisher Item Identifier
Rights:	© the author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	14 Jun 2018 13:13
Last Modified:	14 Jun 2018 13:13
URI:	https://irep.ntu.ac.uk/id/eprint/33856

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