BOLL-Containing Aggregates Mediate the Translational Regulation During Human Oogenesis

Abstract

Human oocyte meiosis utilises a specialised translational control strategy to coordinate meiotic progression, mediated through dynamic regulation of mRNA stores. While germ cell-specific RNA-binding proteins (RBPs) are known to orchestrate this post-transcriptional programme, the mechanistic basis of RBP-mediated cell fate specification remains elusive. Here, we demonstrate that BOLL, a Deleted in Azoospermia (DAZ) family protein, forms protein aggregates during meiotic prophase to drive translational reprogramming in human oogenesis. We determined that BOLL enhances the translation efficiency of cell cycle regulators, as demonstrated by integrative translatome-transcriptome analysis combined with RNA immunoprecipitation sequencing. We also revealed the functional interaction network of BOLL with core translation machinery components through its conserved DAZ-containing domain. Crucially, we identified SDS-resistant protein aggregates as a structural signature of BOLL in human oocyte-like cells, demonstrated by semi-denaturing electrophoretic analysis. Using human foetal ovarian tissues and an hESC-derived oogenesis model, we delineate a paradigm wherein BOLL-containing aggregates exert spatiotemporal control over cell cycle genes during meiosis prophase. These findings reveal that protein aggregates of gametogenesis-specific RBPs constitute an evolutionarily conserved mechanism in mammalian reproductive regulation.

Keywords

human BOLL protein / oogenesis / protein aggregate / translational regulation

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