TENT5C extends Odf1 poly(A) tail to sustain sperm morphogenesis and fertility

Changes in the poly(A) tail length of Odf1 and other transcripts critical for male fertility have been linked to translational activation during sperm formation 1-3. 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 4,5. 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 Odf1 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 6. We propose that TENT5C poly(A) polymerase activity regulates the spatial translation of Odf1 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.