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

T. Kantidakis, R.J. White

Research output: Contribution to journalArticlepeer-review

Abstract

Dr1 (also known as NC2β) 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 NC2α). 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.
Original languageEnglish
Pages (from-to)1228-1239
Number of pages12
JournalNucleic Acids Research
Volume38
Issue number4
Early online date3 Dec 2009
DOIs
Publication statusPublished - 4 Mar 2010

Keywords

  • Animals
  • Cricetulus
  • Humans
  • RNA Polymerase III
  • Transcription Factor TFIIIB
  • Transcription, Genetic
  • RNA, Transfer
  • Transcription Factors
  • Phosphoproteins
  • Repressor Proteins
  • CHO Cells
  • Gene Expression Regulation
  • RNA Interference
  • Cell Line
  • Cricetinae

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