99: NXT2: a testis-specific RNA export hub essential for human spermatogenesis

Dicke A-K et al., Nature Communications - Proteomics, molecular and genetic analyses identify NXT2 as the predominant NXT protein in the human testis that binds NXF1, NXF2 and NXF3 and associates with nucleoporins. Loss-of-function variants in NXT2 are linked to azoospermia with Sertoli cell-only testes, while an NXF3 LoF causes severe sperm defects. Key terms: NXT2, NXF3, RNA export, azoospermia, spermatogenesis. Study Highlights:Proteomic pulldowns from adult human testis reveal NXT2 enrichment together with NXF1, testis-specific paralogs NXF2 and NXF3, and multiple nucleoporins, suggesting a testis-adapted mRNA export complex. Co-immunoprecipitation and deletion mapping show binding between NXT2 and NXF2/NXF3 is mediated by NTF2-like domains. Rare hemizygous loss-of-function variants or deletion of NXT2 were found in infertile men with non-obstructive azoospermia and predominant Sertoli cell-only histology, and an NXF3 stop-gain variant is associated with extreme oligoasthenoteratozoospermia. Functional assays in cells and tissue staining corroborate absent or truncated protein expression and link disrupted NXT2/NXF3 activity to impaired germ cell development and spermatogenesis. Conclusion:NXT2 is a testis-enriched core component of a human testis-adapted RNA nuclear export factor complex and loss of NXT2 function is strongly associated with disrupted germ cell development and male infertility. Music:Enjoy the music based on this article at the end of the episode. Article title:NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis First author:Dicke A-K Journal:Nature Communications DOI:10.1038/s41467-025-61463-0 Reference:Dicke A-K, 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. Nature Communications. 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/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/ep99-nxt2-testis-rna-export QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-08-07. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the portions of the transcript that describe (1) the baseline RNA export pathway, (2) the NXT2-centered testis-specific export complex with NXF2/NXF3 and nucleoporins, (3) the genetic evidence from MERGE/Nijmegen cohorts linking NXT2 LoF to azoospermia and SCO, (4) the NXF3 LoF case and its phenotype, (5) LOEUF- transcript topics: NXT2 as a testis-specific RNA export component; NXT2 interaction with NXF2 and NXF3 via NTF2-like domains; NXT2 predominance in adult human testis vs NXT1; Genetic evidence: NXT2 loss-of-function variants associated with azoospermia and Sertoli cell-only histology; NXF3 loss-of-function and extreme oligoasthenoteratozoospermia; Temporal expression: NXT2 in fetal germ cells; NXF3 in post-meiotic germ cells QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 6- claims flagged for review: 0- met...