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A novel nuclear RNA export pathway in the human testis – NXT2 is key player and azoospermia candidate gene

ABSTRACT: In eukaryotic cells, the nucleocytoplasmic export of bulk poly(A)+-mRNAs through the nuclear pore complex is mediated by the ubiquitously expressed NXT1-NXF1 heterodimer. In humans, autosomal NXT1 has an X-chromosomal paralogue called NXT2, which was subject to adaptive selection in primates and exhibits testis enriched expression, suggesting a role in spermatogenesis. Here, we report on the in vivo interactome of NXT2 in the human adult testis and demonstrate a specific association with key components of the nuclear export machinery, including not only NXF1 but also the testis-specifically expressed NXF1 paralogues NXF2 and NXF3 and nuclear pore complex proteins NUP93 and NUP214. By identifying infertile men with loss-of-function variants in NXT2 and NXF3, we link the impaired NXT2-NXF interactome to disturbed germ cell maturation. The concordantly observed absence of germ cells in the patient affected by NXT2 variants suggests an NXT2-mediated function in early stages of spermatogenesis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Testis

SUBMITTER: Lin Ma

LAB HEAD: Birgit Stallmeyer

PROVIDER: PXD052904 | Pride | 2024-07-25

REPOSITORIES: Pride

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			Action	DRS
	231208_IgG_1.msf	Msf
	231208_IgG_1.raw	Raw
	231208_IgG_2.msf	Msf
	231208_IgG_2.raw	Raw
	231208_NXT2_1.msf	Msf

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