The 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies

Hidefumi Suzuki, Ryota Abe, Miho Shimada, Tomonori Hirose, Hiroko Hirose, Keisuke Noguchi, Yoko Ike, Nanami Yasui, Kazuki Furugori, Yuki Yamaguchi, Atsushi Toyoda, Yutaka Suzuki, Tatsuro Yamamoto, Noriko Saitoh, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, Hidehisa Takahashi

Research output: Contribution to journalArticlepeer-review

Abstract

Non-polyadenylated mRNAs of replication-dependent histones (RDHs) are synthesized by RNA polymerase II (Pol II) at histone locus bodies (HLBs). HLBs frequently associate with Cajal bodies (CBs), in which 3′-end processing factors for RDH genes are enriched; however, this association’s role in transcription termination of RDH genes remains unclear. Here, we show that Pol II pauses immediately upstream of transcript end sites of RDH genes and Mediator plays a role in this Pol II pausing through CBs’ association with HLBs. Disruption of the Mediator docking site for Little elongation complex (LEC)–Cap binding complex (CBC)–Negative elongation factor (NELF), components of CBs, interferes with CBs’ association with HLBs and 3′ Pol II pausing, resulting in increased aberrant unprocessed RDH gene transcripts. Our findings suggest Mediator’s involvement in CBs’ association with HLBs to facilitate 3′ Pol II pausing and subsequent 3′-end processing of RDH genes by supplying 3′-end processing factors.

Original languageEnglish (US)
Article number2905
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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