PAN2 Maintains mRNA PolyA Tail Homeostasis and Regulates Translation during Spermiogenesis in Mouse

Elongation and shortening of the polyA tail are the most common type of post-transcriptional mRNA regulation in eukaryotic cells. Two protein complexes, PAN2-PAN3 and CCR4-NOT, are major cytoplasmic deadenylases that trim the mRNA polyA tails. While PAN2-PAN3 removes the distal portion of the long polyA tails, CCR4-NOT removes adenosine closer to the 3'-UTR. Some subunits in the CCR4-NOT complex have been shown to play synergistic biochemical functions during mouse germ cell development. However, the in vivo functions of the upstream deadenylase PAN2-PAN3 remain unclear, particularly in mammals. In this study, we found that germline-specific deletion of Pan2 leads to male infertility. Pan2 knockout did not affect the prophase of meiosis I, but led to abnormal spermiogenesis and apoptosis of male germ-cells. By Palso-seq and Ribo-lite, we found that the deletion of Pan2 increased the number of long-tail mRNAs in spermiogenesis and disrupted the translation efficiency of genes that should be highly translated at this stage. These findings highlight the crucial physiological functions of PAN2 in gametogenesis and expand our understanding of the posttranscriptional regulation of mRNAs in specific physiological processes. Overall design: MII stage spermatocytes and round spermatids form Pan2flox/-;Stra8-Cre mice were subjected to RNA-seq using the Smart-seq2 method with minor modifications.