A1 Refereed original research article in a scientific journal
SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis
Authors: Lehtiniemi Tiina, Bourgery Matthieu, Ma Lin, Ahmedani Ammar, Mäkelä Margareeta, Asteljoki Juho, Olotu Opeyemi, Laasanen Samuli, Zhang Fu-Ping, Tan Kun, Chousal Jennifer N, Burow Dana, Koskinen Satu, Laiho Asta, Elo Laura L, Chalmel Frédéric, Wilkinson Miles F, Kotaja Noora
Publisher: Oxford Univ Press
Publication year: 2022
Journal: Nucleic Acids Research
Journal name in source: NUCLEIC ACIDS RESEARCH
Journal acronym: NUCLEIC ACIDS RES
Volume: 50
Issue: 20
First page : 11470
Last page: 11491
Number of pages: 22
ISSN: 0305-1048
eISSN: 1362-4962
DOI: https://doi.org/10.1093/nar/gkac900
Web address : https://doi.org/10.1093/nar/gkac900
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/177369224
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3 ' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.
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