️ Episode 99: NXT2: A Testis-Specific RNA Export Factor Essential for Spermatogenesis

In this episode of PaperCast Base by Base, we explore how the testis-enriched paralog NXT2 orchestrates nucleocytoplasmic mRNA export in human germ cells and its critical role in male infertility.

Study Highlights:

Proteomic analyses of human testicular tissue uncovered a specialized interactome of NXT2 that associates with nuclear export factors NXF1, NXF2, and NXF3 as well as nuclear pore components. Domain deletion and co-immunoprecipitation studies demonstrated that NXT2 binds testis-specific NXF paralogs via its NTF2-like domain. Genetic screening of large cohorts of infertile men revealed loss-of-function NXT2 variants that result in Sertoli cell-only phenotypes and azoospermia. Comparative analyses of NXF3 variants highlighted stage-specific roles of the NXT2-NXF3 complex in late spermatogenesis leading to severe oligoasthenoteratozoospermia. These findings illustrate a tailored RNA export pathway pivotal for human germ cell development.

Conclusion:

NXT2 emerges as a crucial candidate gene for male infertility and highlights the importance of testis-specific nuclear export pathways for germ cell development.

Reference:

Dicke AK, Ahmedani A, Ma L, Herrmann L, van der Heijden GW, Koser SA, Krallmann C, Kalyon O, Xavier MJ, Veltman JA, Kliesch S, Neuhaus N, Kotaja N, Tüttelmann F, Stallmeyer B. NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis. Nat Commun. 2025;16:6254. doi:10.1038/s41467-025-61463-0

License:

This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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