ArticleProceedings of the National Academy of Sciences of the United States of America2016
Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 75 citations in OpenAlex.
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- Discordant effects of maternal age on the human MII oocyte transcriptome.Molecular human reproduction · 2025Article
- Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction.Cell communication and signaling : CCS · 2025Article
- RpL38 modulates germ cell differentiation by controlling Bam expression in Drosophila testis.Science China. Life sciences · 2024Article
- Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.eLife · 2024Article
- Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.bioRxiv : the preprint server for biology · 2023Article
- Zishen Yutai Pill improves sperm quality and reduces testicular inflammation in experimental varicocele rats.Heliyon · 2023Article
- The In Vitro Evaluation of Rooster Semen Pellets Frozen with Dimethylacetamide.Animals : an open access journal from MDPI · 2023Article
- SIRT3 inhibition suppresses hypoxia-inducible factor 1α signaling and alleviates hypoxia-induced apoptosis of type B spermatogonia GC-2 cells.FEBS open bio · 2023Article
- Effect of Dimethylacetamide Concentration on Motility, Quality, Antioxidant Biomarkers, Anti-Freeze Gene Expression, and Fertilizing Ability of Frozen/Thawed Rooster Sperm.Animals : an open access journal from MDPI · 2022Article
- Hepatitis, testicular degeneration, and ataxia in DIDO3-deficient mice with altered mRNA processing.Cell & bioscience · 2022Article
- Hepatitis, testicular degeneration, and ataxia in DIDO3-deficient mice with altered mRNA processing.Cell & bioscience · 2022Article
- Studying the mechanism of sperm DNA damage caused by folate deficiency.Journal of cellular and molecular medicine · 2022Article
- Genome-Wide Association Studies, Runs of Homozygosity Analysis, and Copy Number Variation Detection to Identify Reproduction-Related Genes in Bama Xiang Pigs.Frontiers in veterinary science · 2022Article
- Phylogeny and conservation of plant U2A/U2A', a core splicing component in U2 spliceosomal complex.Planta · 2021Article
- Strategies to Identify Genetic Variants Causing Infertility.Trends in molecular medicine · 2021Review
- Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes.Cell death discovery · 2021Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Processing of pre-mRNA into mRNA is an important regulatory mechanism in eukaryotes that is mediated by the spliceosome, a huge and dynamic ribonucleoprotein complex. Splicing defects are implicated in a spectrum of human disease, but the underlying mechanistic links remain largely unresolved. Using a genome-wide association approach, we have recently identified single nucleotide polymorphisms in humans that associate with nonobstructive azoospermia (NOA), a common cause of male infertility. Here, using genetic manipulation of corresponding candidate loci in Drosophila, we show that the spliceosome component SNRPA1/U2A is essential for male fertility. Loss of U2A in germ cells of the Drosophila testis does not affect germline stem cells, but does result in the accumulation of mitotic spermatogonia that fail to differentiate into spermatocytes and mature sperm. Lack of U2A causes insufficient splicing of mRNAs required for the transition of germ cells from proliferation to differentiation. We show that germ cell-specific disruption of other components of the major spliceosome manifests with the same phenotype, demonstrating that mRNA processing is required for the differentiation of spermatogonia. This requirement is conserved, and expression of human SNRPA1 fully restores spermatogenesis in U2A mutant flies. We further report that several missense mutations in human SNRPA1 that inhibit the assembly of the major spliceosome dominantly disrupt spermatogonial differentiation in Drosophila. Collectively, our findings uncover a conserved and specific requirement for the major spliceosome during the transition from spermatogonial proliferation to differentiation in the male testis, suggesting that spliceosome defects affecting the differentiation of human spermatogonia contribute to NOA.
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