NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis
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 spermatoge...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61463-0 |
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| author | Ann-Kristin Dicke Ammar Ahmedani Lin Ma Leonie Herrmann Godfried W. van der Heijden Sophie A. Koser Claudia Krallmann Oguzhan Kalyon Miguel J. Xavier Joris A. Veltman Sabine Kliesch Nina Neuhaus Noora Kotaja Frank Tüttelmann Birgit Stallmeyer |
| author_facet | Ann-Kristin Dicke Ammar Ahmedani Lin Ma Leonie Herrmann Godfried W. van der Heijden Sophie A. Koser Claudia Krallmann Oguzhan Kalyon Miguel J. Xavier Joris A. Veltman Sabine Kliesch Nina Neuhaus Noora Kotaja Frank Tüttelmann Birgit Stallmeyer |
| author_sort | Ann-Kristin Dicke |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-35ef1f0cfb2f49fa8b3f95c73b54a913 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-35ef1f0cfb2f49fa8b3f95c73b54a9132025-08-20T04:03:07ZengNature PortfolioNature Communications2041-17232025-07-0116111710.1038/s41467-025-61463-0NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesisAnn-Kristin Dicke0Ammar Ahmedani1Lin Ma2Leonie Herrmann3Godfried W. van der Heijden4Sophie A. Koser5Claudia Krallmann6Oguzhan Kalyon7Miguel J. Xavier8Joris A. Veltman9Sabine Kliesch10Nina Neuhaus11Noora Kotaja12Frank Tüttelmann13Birgit Stallmeyer14Institute of Reproductive Genetics, Centre of Medical Genetics, University of MünsterInstitute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of TurkuInstitute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of TurkuInstitute of Reproductive Genetics, Centre of Medical Genetics, University of MünsterDivision of Reproductive Medicine, Department of Obstetrics and GynecologyInstitute of Reproductive Genetics, Centre of Medical Genetics, University of MünsterCentre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital MünsterBiosciences Institute, Faculty of Medical Sciences, Newcastle UniversityBiosciences Institute, Faculty of Medical Sciences, Newcastle UniversityBiosciences Institute, Faculty of Medical Sciences, Newcastle UniversityCentre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital MünsterCentre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital MünsterInstitute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of TurkuInstitute of Reproductive Genetics, Centre of Medical Genetics, University of MünsterInstitute of Reproductive Genetics, Centre of Medical Genetics, University of MünsterAbstract 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.https://doi.org/10.1038/s41467-025-61463-0 |
| spellingShingle | Ann-Kristin Dicke Ammar Ahmedani Lin Ma Leonie Herrmann Godfried W. van der Heijden Sophie A. Koser Claudia Krallmann Oguzhan Kalyon Miguel J. Xavier Joris A. Veltman Sabine Kliesch Nina Neuhaus Noora Kotaja Frank Tüttelmann Birgit Stallmeyer NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis Nature Communications |
| title | NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis |
| title_full | NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis |
| title_fullStr | NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis |
| title_full_unstemmed | NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis |
| title_short | NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis |
| title_sort | nxt2 is a key component of the rna nuclear export factor complex in the human testis and essential for spermatogenesis |
| url | https://doi.org/10.1038/s41467-025-61463-0 |
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