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

Abstract

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 Zcchc8 null testes. Further study found that a reduced H3K9me3 modification in SSC and elevated H3 lysine 4 trimethylation in the PS of Zcchc8 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.