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Reproductive sciences (Thousand Oaks, Calif.) · 2026

The Role of RNA Interactions with PIWI in Regulating Gametogenesis, Fertilization, and Early Development Across Species.

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Haddadi Mahnaz, Safari-Alighiarloo Nahid, Mikaeeli Gelareh, Meftagh Mohadeseh Sadat, Jazayeri Maryam

Аннотация

Small RNA-mediated regulatory systems maintain DNA integrity and proper functioning of the germ cell lineage. One such system consists of P-element-induced wimpy testis (PIWI) proteins and PIWI-interacting RNAs (piRNAs). Researchers initially identified piRNAs as repressors of transposable elements. Subsequent studies have identified additional roles, including regulating epigenetic programming, maintaining maternal transcript homeostasis and controlling processes involved in early embryonic development. Comparative studies of piRNAs and their functions across species have revealed substantial differences, including sex- and species-specific patterns of piRNA expression, differences in piRNA cluster organization, and functional diversity among PIWI proteins. These differences may reflect the diverse reproductive strategies and evolutionary adaptations of the species examined. Disruption of the piRNA pathway has been associated with infertility and germ-cell tumors in various studies; however, the species involved and the nature of these associations (e.g., mechanistic vs. correlative) require further investigation. These findings indicate a need for further study of piRNA regulation at the cellular level and its clinical relevance to reproductive biology. This review examines the biogenesis and biological functions of PIWI/piRNA complexes, compares PIWI/piRNA biology across species, evaluates conserved and species-specific aspects of these processes, and identifies important questions that remain underexplored in the literature.