Coprs inactivation leads to a derepression of LINE1 transposons in spermatocytes

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 pi RNA 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 spectrometry analysis revealed the presence of Miwi in testis protein lysates immunoprecipitated with an anti‐Coprs antibody. The observed deregulation of Miwi and pachytene pre‐pi RNA s levels and the derepression of LINE 1 repetitive sequences observed in coprs ‐/‐ mice suggest that Coprs is implicated in genome surveillance mechanisms.

Factors Regulating the Activity of LINE1 Retrotransposons

“…Knockout of the Fancd2 factor leads to a decrease in Fancd2-catalyzed H2A/H4R3me2s markers in the L1 region at E10.5 [188]. Additionally, Corps factor (Copr5) is required to activate Prmt5 [189,190]. In mice PGS, Mili protein expression begins from E12.5 and lasts the longest until around the spermatid stage in adult testicles [190,191].…”

“…Additionally, Corps factor (Copr5) is required to activate Prmt5 [189,190]. In mice PGS, Mili protein expression begins from E12.5 and lasts the longest until around the spermatid stage in adult testicles [190,191]. Mili is located mainly in the cytoplasm and is required for the primary processing of piRNA, secondary piRNA biogenesis, the ping-pong cycle, de novo DNA methylation, and posttranscriptional inhibition of L1 retrotransposons [180,192].…”

“…Recently, it was shown that at the prophase stage of meiosis I, Uhrf1 is necessary for the interaction with Prmt5 and activation of PIWI proteins at the pachytene stage, and its absence leads to the activation of L1 and AIP retrotransposons, resulting in a decrease in DNA and histone methylation, as well as a deficiency in the piRNA/PIWI-signaling pathway, leading to defective meiosis and sterility [130,211]. It has also recently been shown that in adult testicles, Corps is required for Prmt5 activation and its knockout leads to a decrease in Miwi and L1 activation, disrupting the maturation of spermatogonia in spermatids and leading to infertility [190]. At the pachytene stage, many factors participating in the piRNA/PIWI-signaling pathway begin to be expressed, including the Miwi protein, which is characteristic of mature testicles [207,215].…”

“…well as a deficiency in the piRNA/PIWI-signaling pathway, leading to defective meiosis and sterility [130,211]. It has also recently been shown that in adult testicles, Corps is required for Prmt5 activation and its knockout leads to a decrease in Miwi and L1 activation, disrupting the maturation of spermatogonia in spermatids and leading to infertility [190]. At the pachytene stage, many factors participating in the piRNA/PIWI-signaling pathway begin to be expressed, including the Miwi protein, which is characteristic of mature testicles [207,215].…”