Coprs inactivation leads to a derepression of LINE1 transposons in spermatocytes. Issue 1 (19th December 2018)

• Record Type: Journal Article
• Authors: Paul, Conception; Delpech, Hélène; Haouzi, Delphine; Hamamah, Samir; Sardet, Claude; Fabbrizio, Eric
• Is Part Of: FEBS open bio. Volume 9:Issue 1(2019)
• Page Start: 159
• Page End: 168
• Publication Date: 2018-12-19
• Subjects: coprs -- Miwi -- piRNA -- spermatocyte -- teratozoospermia -- testis; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12562
• Languages: English
• ISSNs: 2211-5463

Abstract

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 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‐piRNAs levels and the derepression of LINE1 repetitive sequences observed in coprs ‐/‐ mice suggest that Coprs is implicated in genome surveillance mechanisms. Abstract : During spermiogenesis, a functional Miwi‐piRNA pathway is critical to safeguard genome integrity. Of the Miwi‐associated pachytene Piwi‐interacting RNAs (piRNAs), it is repeat‐derived piRNAs which guide Miwi slicer activity to silence transposon transcripts. Miwi was co‐immunoprecipitated with Coprs, and expression of both Miwi and piRNAs is downregulated in coprs KO mouse through unknown transcriptional and/or post‐transcriptional mechanisms, leading to LINE1 accumulation and delayed spermatogenesis.