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

Abstract 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 unclear 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, Odf1 transcripts show shorter poly(A) tails and, together with ODF1 protein, fail to accumulate at the spermatid neck. Mice expressing a catalytically inactive TENT5C produce headless spermatozoa with flagellar abnormalities associated with ODF1 deficiency 6 . We propose that TENT5C poly(A) polymerase activity regulates the stability and local translation of Odf1 mRNAs at the neck of late-stage spermatids, 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.