Baptissart Marine, Gupta Ankit, Poirot Alexander C, Papas Brian N, Morgan Marcos
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina 27709, USA.
Integrative Bioinformatics, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina 27709, USA.
bioRxiv. 2025 Mar 24:2025.03.20.644152. doi: 10.1101/2025.03.20.644152.
Changes in the poly(A) tail length of and other transcripts critical for male fertility have been linked to translational activation during sperm formation . The mRNA poly(A) polymerase TENT5C is required for fastening the flagellum to the sperm head, but its role in shaping the poly(A) tail profile of the spermatid transcriptome remains limited . Here, we comprehensively document how changes in mRNA poly(A) tail length across the transcriptome reflect transcript metabolism in spermatids. In the absence of TENT5C polymerase activity, the poly(A) tail length of transcripts is reduced, and the local distribution of ODF1 proteins in spermatids is disrupted. We show that mice expressing a catalytically inactive TENT5C produce headless spermatozoa with outer dense fibers detached from the axoneme, and other flagellar abnormalities associated with ODF1 deficiency . We propose that TENT5C poly(A) polymerase activity regulates the spatial translation of mRNAs during spermiogenesis, a process critical for sperm morphogenesis and fertility. These findings highlight the power of poly(A) tail profiling to identify abnormal mRNA processing causative of infertility.
精子形成过程中，与雄性生育力至关重要的 及其他转录本的聚腺苷酸（poly(A)）尾长度变化与翻译激活有关。mRNA 聚腺苷酸聚合酶 TENT5C 是将鞭毛固定在精子头部所必需的，但它在塑造精子细胞转录组的聚腺苷酸尾图谱方面的作用仍然有限。在这里，我们全面记录了整个转录组中 mRNA 聚腺苷酸尾长度的变化如何反映精子细胞中的转录本代谢。在缺乏 TENT5C 聚合酶活性的情况下， 转录本的聚腺苷酸尾长度缩短，精子细胞中 ODF1 蛋白的局部分布受到破坏。我们表明，表达无催化活性 TENT5C 的小鼠产生无头精子，其外致密纤维与轴丝分离，以及其他与 ODF1 缺乏相关的鞭毛异常。我们提出，TENT5C 聚腺苷酸聚合酶活性在精子发生过程中调节 mRNA 的空间翻译，这一过程对精子形态发生和生育力至关重要。这些发现突出了聚腺苷酸尾分析在识别导致不育的异常 mRNA 加工方面的作用。
