BEND3 represses rDNA transcription by stabilizing a NoRC component via USP21 deubiquitinase

Abid Khan, Sumanprava Giri, Yating Wang, Arindam Chakraborty, Archit K. Ghosh, Aparna Anantharaman, Vasudha Aggarwal, Kizhakke M. Sathyan, Taekjip Ha, Kannanganattu V. Prasanth, Supriya G. Prasanth

Research output: Contribution to journalArticlepeer-review

Abstract

Ribosome biogenesis dictates the translational capacity of cells. Several mechanisms establish and maintain transcriptional output from eukaryotic ribosomal DNA (rDNA) loci. rDNA silencing is one such mechanism that ensures the inactivity and hence the maintenance of a silenced state of a subset of rRNA gene copies. Whereas oncogenic agents stimulate rRNA gene transcription, tumor suppressors decrease rRNA gene transcription. We demonstrate in mammalian cells that BANP, E5R, and Nac1 (BEN) domain 3 (BEND3), a quadruple BEN domain-containing protein, localizes in nucleoli and binds to ribosomal RNA gene promoters to help repress rRNA genes. Loss of BEND3 increases histone H3K4 trimethylation and, correspondingly, decreases rDNA promoter DNA methylation, consistent with a role for BEND3 in rDNA silencing. BEND3 associates with the nucleolar-remodeling complex (NoRC), and SUMOylated BEND3 stabilizes NoRC component TTF-1-interacting protein 5 via association with ubiquitin specific protease 21 (USP21) debiquitinase. Our results provide mechanistic insights into how the novel rDNA transcription repressor BEND3 acts together with NoRC to actively coordinate the establishment of rDNA silencing.

Original languageEnglish (US)
Pages (from-to)8338-8343
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number27
DOIs
StatePublished - Jul 7 2015
Externally publishedYes

Keywords

  • BEND3
  • NoRC
  • Tip5
  • Transcription repression
  • rDNA

ASJC Scopus subject areas

  • General

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