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NKAPL facilitates transcription pause-release and bridges elongation to initiation during meiosis exit

Author

Listed:
  • Zhenlong Kang

    (Nanjing Medical University)

  • Chen Xu

    (Nanjing Medical University)

  • Shuai Lu

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

  • Jie Gong

    (Nanjing Medical University)

  • Ruoyu Yan

    (Nanjing Medical University)

  • Gan Luo

    (Nanjing Medical University)

  • Yuanyuan Wang

    (Nanjing Medical University)

  • Qing He

    (Nanjing Medical University)

  • Yifei Wu

    (Nanjing Medical University)

  • Yitong Yan

    (Nanjing Medical University)

  • Baomei Qian

    (University of Science and Technology of China)

  • Shenglin Han

    (Nanjing Medical University)

  • Zhiwen Bu

    (Nanjing Medical University)

  • Jinwen Zhang

    (Nanjing Medical University)

  • Xian Xia

    (Nanjing Medical University)

  • Liang Chen

    (Wuhan University)

  • Zhibin Hu

    (Nanjing Medical University
    Nanjing Medical University)

  • Mingyan Lin

    (Nanjing Medical University)

  • Zheng Sun

    (Baylor College of Medicine)

  • Yayun Gu

    (Nanjing Medical University
    Gusu School
    Innovation Center of Suzhou Nanjing Medical University
    National Center of Technology Innovation for Biopharmaceuticals)

  • Lan Ye

    (Nanjing Medical University
    Innovation Center of Suzhou Nanjing Medical University
    National Center of Technology Innovation for Biopharmaceuticals)

Abstract

Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes. NKAPL binds to promoter-associated nascent transcripts and co-localizes with DNA-RNA hybrid R-loop structures at GAA-rich loci to enhance R-loop formation and facilitate Pol II pause-release. NKAPL depletion prolongs Pol II pauses and stalls the SOX30/HDAC3 transcription initiation complex on the chromatin. Genetic variants in NKAPL are associated with azoospermia in humans, while mice carrying an NKAPL frameshift mutation (M349fs) show defective meiotic exit and transcriptomic changes similar to NKAPL depletion. These findings identify NKAPL as an R-loop-recognizing factor that regulates transcription elongation, which coordinates the meiotic-to-postmeiotic transcriptome switch in alliance with the SOX30/HDAC3-mediated transcription initiation.

Suggested Citation

  • Zhenlong Kang & Chen Xu & Shuai Lu & Jie Gong & Ruoyu Yan & Gan Luo & Yuanyuan Wang & Qing He & Yifei Wu & Yitong Yan & Baomei Qian & Shenglin Han & Zhiwen Bu & Jinwen Zhang & Xian Xia & Liang Chen & , 2025. "NKAPL facilitates transcription pause-release and bridges elongation to initiation during meiosis exit," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55579-y
    DOI: 10.1038/s41467-024-55579-y
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    References listed on IDEAS

    as
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