TY - JOUR
T1 - The 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies
AU - Suzuki, Hidefumi
AU - Abe, Ryota
AU - Shimada, Miho
AU - Hirose, Tomonori
AU - Hirose, Hiroko
AU - Noguchi, Keisuke
AU - Ike, Yoko
AU - Yasui, Nanami
AU - Furugori, Kazuki
AU - Yamaguchi, Yuki
AU - Toyoda, Atsushi
AU - Suzuki, Yutaka
AU - Yamamoto, Tatsuro
AU - Saitoh, Noriko
AU - Sato, Shigeo
AU - Tomomori-Sato, Chieri
AU - Conaway, Ronald C.
AU - Conaway, Joan W.
AU - Takahashi, Hidehisa
N1 - Funding Information:
We thank Miho Uchiumi for help in preparing the manuscript, Naomichi Matsumoto for providing us with BAC DNA clones and Tetsuro Kokubo for helpful discussions. We also thank Edanz ( https://jp.edanz.com/ac ) for editing a draft of this manuscript. This work was supported in part by KAKENHI [2020K15718 to H.S., 16H06279 (PAGS), 17K19578, 221S0002, 18H02378, 19K22401, 21H05159, 21H02405, and 21K19356 to H.T.] and by Takeda Science Foundation (H.T.), Suhara Memorial Fund (H.T.), Takamatsu Cancer Research Fund (H.T.), Leukemia Research Fund (H.T.), The Ichiro Kanehara Foundation (H.T.), Friends of Leukemia Research Fund (H.T.), Ono Cancer Research Fund (H.T.), Kobayashi Foundation for Cancer Research (H.T.), MSD Life Science Foundation (H.T.), The Naito Foundation (H.T.), The Tokyo Biochemical Research Foundation (H.T.), Yokohama Foundation for Advancement of Medical Science (H.T.), Nakatani Foundation (H.T.) and by a grant from the Helen Nelson Medical Research Fund to the Stowers Institute (J.W.C.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30632-w
DO - 10.1038/s41467-022-30632-w
M3 - Article
C2 - 35614107
AN - SCOPUS:85130763367
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2905
ER -