Germline piRNAs counteract endogenous retrovirus invasion from somatic cells

Abstract

AbstractIn metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERV ZAM in somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somatic flamenco piRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation, ZAM invaded the oocytes, resulting in transposition and severe fertility defects. We show that once ZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity.