IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-61463-0.html
   My bibliography  Save this article

NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis

Author

Listed:
  • Ann-Kristin Dicke

    (University of Münster)

  • Ammar Ahmedani

    (University of Turku)

  • Lin Ma

    (University of Turku)

  • Leonie Herrmann

    (University of Münster)

  • Godfried W. Heijden

    (Department of Obstetrics and Gynecology)

  • Sophie A. Koser

    (University of Münster)

  • Claudia Krallmann

    (University Hospital Münster)

  • Oguzhan Kalyon

    (Newcastle University)

  • Miguel J. Xavier

    (Newcastle University)

  • Joris A. Veltman

    (Newcastle University
    University of Edinburgh)

  • Sabine Kliesch

    (University Hospital Münster)

  • Nina Neuhaus

    (University Hospital Münster)

  • Noora Kotaja

    (University of Turku)

  • Frank Tüttelmann

    (University of Münster)

  • Birgit Stallmeyer

    (University of Münster)

Abstract

In eukaryotes, the nucleocytoplasmic export of bulk poly(A)+-mRNAs through the nuclear pore complex is mediated by the ubiquitously expressed NXT1-NXF1 heterodimer. In humans, NXT1 has an X-chromosomal paralog, NXT2, which exhibits testis-enriched expression, suggesting a role in spermatogenesis. Here, we report the in vivo interaction of NXT2 with crucial components of the nuclear export machinery, including NXF1, the testis-specific NXF1 paralogs NXF2 and NXF3, and nuclear pore complex proteins. Binding to NXF2 and NXF3 is mediated by the NTF2-like domain of NXT2. By identifying infertile men with loss-of-function variants in NXT2 and NXF3, we link the impaired NXT2-NXF activity to disturbed germ cell development. The predominant absence of germ cells in men with NXT2 deficiency indicates its critical function already during fetal or first steps of germ cell development. In contrast, loss of NXF3 affects later stages of spermatogenesis, resulting in quantitatively and qualitatively impaired sperm production.

Suggested Citation

  • Ann-Kristin Dicke & Ammar Ahmedani & Lin Ma & Leonie Herrmann & Godfried W. Heijden & Sophie A. Koser & Claudia Krallmann & Oguzhan Kalyon & Miguel J. Xavier & Joris A. Veltman & Sabine Kliesch & Nina, 2025. "NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61463-0
    DOI: 10.1038/s41467-025-61463-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-61463-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-61463-0?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-61463-0. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.