Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells

Kantidakis, T. and White, R.J. (2010) Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells. Nucleic Acids Research, 38(4), pp. 1228-1239. (doi: 10.1093/nar/gkp1102)

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Abstract

Dr1 (also known as NC2{beta}) was identified as a repressor of RNA polymerase (pol) II transcription. It was subsequently shown to inhibit pol III transcription when expressed at high levels in vitro or in yeast cells. However, endogenous Dr1 was not detected at pol III-transcribed genes in growing yeast. In contrast, we demonstrate that endogenous Dr1 is present at pol III templates in human cells, as is its dimerization partner DRAP1 (also called NC2{alpha}). Expression of tRNA by pol III is selectively enhanced by RNAi-mediated depletion of endogenous human Dr1, but we found no evidence that DRAP1 influences pol III output in vivo. A stable association was detected between endogenous Dr1 and the pol III-specific transcription factor Brf1. This interaction may recruit Dr1 to pol III templates in vivo, as crosslinking to these sites increases following Brf1 induction. On the basis of these data, we conclude that the physiological functions of human Dr1 include regulation of pol III transcription.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:White, Prof Robert and Kantidakis, Dr Theodoros
Authors: Kantidakis, T., and White, R.J.
Subjects:Q Science > QH Natural history > QH426 Genetics
Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nucleic Acids Research
Publisher:Oxford University Press
ISSN:0305-1048
ISSN (Online):1362-4962
Published Online:09 December 2009
Copyright Holders:Copyright © 2009 The Authors
First Published:First published in Nucleic Acids Research 38(4):1228-1239
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
364461The involvement of RNA polymerases I and III in cancerRobert WhiteCancer Research UK (CAN-RES-UK)C1288/A4411Institute of Cancer Sciences