TBPL2-dependent transcription controls RNA stability and cellular organization in growing oocytes

Abstract

During oocyte growth, the marked increase in cell size is accompanied by robust RNA polymerase II (Pol II) transcription, generating transcripts that are either translated into proteins or stored as part of the maternal transcriptome. While the RNA decay machinery is known to critically regulate the maternal transcriptome during oocyte maturation, its contribution during the growth phase remains poorly understood. We previously identified an oocyte-specific transcription machinery dependent on the TATA-binding protein paralog TBPL2, which is required for oocyte growth. To investigate how the absence of TBPL2-mediated transcription affects the cellular state of the oocyte, we characterized the phenotypic consequences of the Tbpl2-/- mutation in growing oocytes. Our data reveal that both nuclear and cytoplasmic organizations are profoundly disrupted in the absence of TBPL2-mediated transcription. Given that cytoplasmic organization is closely linked to RNA storage capacity, we examined the expression and localization of proteins involved in mRNA regulation, stability and storage. We observed a marked impairment in the redistribution of these key factors in Tbpl2-/- oocytes. To assess the impact of TBPL2 on RNA storage, we analyzed poly(A) tail length and found a global increase in polyadenylation in mutant oocytes. Gene-specific poly(A) tail analyses revealed differential mRNA changes, with shortened tails for a downregulated transcript and elongated tails for an upregulated one, suggesting stabilization of the latter. Collectively, our findings indicate that TBPL2-mediated transcription is essential for maintaining proper cellular organization in growing oocytes, at least in part by ensuring the functional integrity of the RNA decay machinery.