Abstract
Repression of retrotransposons is essential for genome integrity during germ cell development and is tightly controlled through epigenetic mechanisms. In primordial germ cells, protein arginine N-methyltransferase (Prmt5) is involved in retrotransposon repression by methylating Piwi proteins , which is part of the piRNA pathway. Here, we show that in mice, genetic inactivation of coprs (which is highly expressed in testis and encodes a histone-binding protein required for the targeting of Prmt5 activity) affects the maturation of spermatogonia to spermatids. Mass spectrom-etry analysis revealed the presence of Miwi in testis protein lysates immunoprecipitated with an anti-Coprs antibody. The observed deregulation of Miwi and pachytene pre-piRNAs levels and the derepression of LINE1 repetitive sequences observed in coprs-/-mice suggest that Coprs is implicated in genome surveillance mechanisms. Spermatogenesis is a multistep process that takes place in the seminiferous tubules whereby mature spermato-zoa are continuously produced during adulthood reproduction lifetime. Specifically, primordial germ cells (PGCs) generate spermatogonia that either self-renew to maintain a pool of stem cells or undergo differentiation. After two meiotic divisions, secondary spermato-cytes are produced. Then, during spermiogenesis, they differentiate into elongating spermatids and finally spermatozoa [1-5]. Importantly, these changes are associated with chromatin compaction, transcription arrest, and specific epigenetic modifications that contribute to the production of mature sperm. Concomi-tantly, to maintain genome integrity, PGCs need to repress repetitive DNA elements because their spread can lead to inherited diseases. These repetitive sequences [for instance, long interspersed nuclear elements 1 (LINEs), short interspersed nuclear element (SINEs), and intracisternal A-particle (IAP) sequences] derive mostly from transposable elements and represent Abbreviations Coprs, coordinator of Prmt5 and differentiation stimulator; IAP, intracisternal A-particle; LINE1, long interspersed nuclear element 1; piRNA, Piwi-interacting RNA; Prmt5, protein arginine N-methyltransferase; SINE, short interspersed nuclear element. 159 FEBS Open Bio 9 (2019) 159-168 ª