Biol Reprod 2025 Oct 14;1134:745-764. doi: 10.1093/biolre/ioaf105.

Navigation of Nanos germ cell specification factor to germ granules-posttranscriptional regulation hubs-across species†.

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NANOS, initially identified in Drosophila melanogaster (fruit fly) as a morphogen essential for body patterning and germ cell development, is a highly conserved ribonucleic acid (RNA)-binding protein critical for germ cell formation across species. NANOS dysfunction leads to infertility from flies to humans. While D. melanogaster has a single Nanos gene, paralogs (Nanos1-3) exist in species like Caenorhabditis elegans (roundworm), Danio rerio (zebrafish), Xenopus laevis (clawed frog), and mammals, each with distinct reproductive roles. Nanos messenger RNA is one of the most conserved components of germ granules, characteristic cytoplasmic ribonucleoprotein condensates found in the cytoplasm of animal germ cells. The germ granules are essential for the posttranscriptional temporal regulation of germ cell specification, development, maintenance, and integrity across species. Their origin, cytoplasmic sub-localizations, structure and shape differ depending on the sex and developmental stage. This review examines the biological significance and dynamics of Nanos within germ granules across various model organisms. A central question is whether NANOS gene mutations linked to infertility drive the remodeling of germ cell granules. This question also extends to other conserved germ granule components discussed in this review. Addressing these issues will enhance our understanding of the molecular mechanisms underlying human infertility.

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