IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45177-3.html
   My bibliography  Save this article

RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis

Author

Listed:
  • Emily G. Kaye

    (Harvard Medical School)

  • Kavyashree Basavaraju

    (University of Illinois Urbana-Champaign)

  • Geoffrey M. Nelson

    (Harvard Medical School)

  • Helena D. Zomer

    (University of Illinois Urbana-Champaign)

  • Debarun Roy

    (University of Illinois Urbana-Champaign)

  • Irene Infancy Joseph

    (University of Illinois Urbana-Champaign)

  • Reza Rajabi-Toustani

    (University of Illinois Urbana-Champaign)

  • Huanyu Qiao

    (University of Illinois Urbana-Champaign)

  • Karen Adelman

    (Harvard Medical School)

  • Prabhakara P. Reddi

    (University of Illinois Urbana-Champaign)

Abstract

Male germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double-strand break (DSB) formation, and disruption of meiotic gene expression and DSB repair in germ cells lacking NELF.

Suggested Citation

  • Emily G. Kaye & Kavyashree Basavaraju & Geoffrey M. Nelson & Helena D. Zomer & Debarun Roy & Irene Infancy Joseph & Reza Rajabi-Toustani & Huanyu Qiao & Karen Adelman & Prabhakara P. Reddi, 2024. "RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45177-3
    DOI: 10.1038/s41467-024-45177-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45177-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45177-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jiexiang Zhao & Ping Lu & Cong Wan & Yaping Huang & Manman Cui & Xinyan Yang & Yuqiong Hu & Yi Zheng & Ji Dong & Mei Wang & Shu Zhang & Zhaoting Liu & Shuhui Bian & Xiaoman Wang & Rui Wang & Shaofang , 2021. "Cell-fate transition and determination analysis of mouse male germ cells throughout development," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Seychelle M. Vos & Lucas Farnung & Marc Boehning & Christoph Wigge & Andreas Linden & Henning Urlaub & Patrick Cramer, 2018. "Structure of activated transcription complex Pol II–DSIF–PAF–SPT6," Nature, Nature, vol. 560(7720), pages 607-612, August.
    3. Adriana K. Alexander & Edward J. Rice & Jelena Lujic & Leah E. Simon & Stephanie Tanis & Gilad Barshad & Lina Zhu & Jyoti Lama & Paula E. Cohen & Charles G. Danko, 2023. "A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Christina Ernst & Nils Eling & Celia P. Martinez-Jimenez & John C. Marioni & Duncan T. Odom, 2019. "Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Roberto Bandiera & Rebecca E. Wagner & Thiago Britto-Borges & Christoph Dieterich & Sabine Dietmann & Susanne Bornelöv & Michaela Frye, 2021. "RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Wu Zuo & Guangming Chen & Zhimei Gao & Shuai Li & Yanyan Chen & Chenhui Huang & Juan Chen & Zhengjun Chen & Ming Lei & Qian Bian, 2021. "Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    3. Shixuan Liu & Camille Ezran & Michael F. Z. Wang & Zhengda Li & Kyle Awayan & Jonathan Z. Long & Iwijn De Vlaminck & Sheng Wang & Jacques Epelbaum & Christin S. Kuo & Jérémy Terrien & Mark A. Krasnow , 2024. "An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    4. Shuwen He & John P. Gillies & Juliana L. Zang & Carmen M. Córdoba-Beldad & Io Yamamoto & Yasuhiro Fujiwara & Julie Grantham & Morgan E. DeSantis & Hiroki Shibuya, 2023. "Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Lisa-Marie Appel & Vedran Franke & Melania Bruno & Irina Grishkovskaya & Aiste Kasiliauskaite & Tanja Kaufmann & Ursula E. Schoeberl & Martin G. Puchinger & Sebastian Kostrhon & Carmen Ebenwaldner & M, 2021. "PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    6. Debashish U. Menon & Oleksandr Kirsanov & Christopher B. Geyer & Terry Magnuson, 2021. "Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    7. Wojciech Barczak & Simon M. Carr & Geng Liu & Shonagh Munro & Annalisa Nicastri & Lian Ni Lee & Claire Hutchings & Nicola Ternette & Paul Klenerman & Alexander Kanapin & Anastasia Samsonova & Nicholas, 2023. "Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Seina Ohe & Yuji Kubota & Kiyoshi Yamaguchi & Yusuke Takagi & Junichiro Nashimoto & Hiroko Kozuka-Hata & Masaaki Oyama & Yoichi Furukawa & Mutsuhiro Takekawa, 2022. "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Saori Yoshimura & Ryuki Shimada & Koji Kikuchi & Soichiro Kawagoe & Hironori Abe & Sakie Iisaka & Sayoko Fujimura & Kei-ichiro Yasunaga & Shingo Usuki & Naoki Tani & Takashi Ohba & Eiji Kondoh & Tomoh, 2024. "Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    10. Jasper Panten & Tobias Heinen & Christina Ernst & Nils Eling & Rebecca E. Wagner & Maja Satorius & John C. Marioni & Oliver Stegle & Duncan T. Odom, 2024. "The dynamic genetic determinants of increased transcriptional divergence in spermatids," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Moïra Rossitto & Stephanie Déjardin & Chris M. Rands & Stephanie Gras & Roberta Migale & Mahmoud-Reza Rafiee & Yasmine Neirijnck & Alain Pruvost & Anvi Laetitia Nguyen & Guillaume Bossis & Florence Ca, 2022. "TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    12. Hironori Abe & Yu-Han Yeh & Yasuhisa Munakata & Kei-Ichiro Ishiguro & Paul R. Andreassen & Satoshi H. Namekawa, 2022. "Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    13. Michael DeBerardine & Gregory T. Booth & Philip P. Versluis & John T. Lis, 2023. "The NELF pausing checkpoint mediates the functional divergence of Cdk9," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Jiexiang Zhao & Ping Lu & Cong Wan & Yaping Huang & Manman Cui & Xinyan Yang & Yuqiong Hu & Yi Zheng & Ji Dong & Mei Wang & Shu Zhang & Zhaoting Liu & Shuhui Bian & Xiaoman Wang & Rui Wang & Shaofang , 2021. "Cell-fate transition and determination analysis of mouse male germ cells throughout development," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    15. Annkatrin Bressin & Olga Jasnovidova & Mirjam Arnold & Elisabeth Altendorfer & Filip Trajkovski & Thomas A. Kratz & Joanna E. Handzlik & Denes Hnisz & Andreas Mayer, 2023. "High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    16. Abdallah Gaballa & Anneli Gebhardt-Wolf & Bastian Krenz & Greta Mattavelli & Mara John & Giacomo Cossa & Silvia Andreani & Christina Schülein-Völk & Francisco Montesinos & Raphael Vidal & Carolin Kast, 2024. "PAF1c links S-phase progression to immune evasion and MYC function in pancreatic carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45177-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.