Core factor of NEXT complex, ZCCHC8, governs the silencing of LINE1 during spermatogenesis.

The overactivation of transposable elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here, we report that zinc finger protein ZCCHC8-a key component of the nuclear exosome targeting (NEXT) complex that is involved in ribonucleic acid (RNA) surveillance-is required for TE silencing during spermatogenesis. Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids (RS). We observed that young long-interspersed nuclear element (LINE1, L1) subfamilies that are targeted by ZCCHC8 were upregulated in both spermatogonial stem cells (SSC) and pachytene spermatocytes (PS) of null testes. Further study found that a reduced H3K9me3 modification in SSC and elevated H3 lysine 4 trimethylation in the PS of KO mice occurred upon young L1, especially L1Md_A, which may have contributed to impairment of the chromatin condensation from PS to RS during spermatogenesis. This study highlights the crucial role of RNA surveillance-mediated chromatin repression by the NEXT complex during spermatogenesis.