MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 26; pp. 11847 - 11852
• Main Authors: Frost, Robert J. A., Hamra, F. Kent, Richardson, James A., Qi, Xiaoxia, Bassel-Duby, Rhonda, Olson, Eric N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29.06.2010; National Acad Sciences
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Argonaute Proteins; Base Sequence; Biological Sciences; Cells; DNA Methylation; DNA Primers - genetics; Fertility; Gene expression; Genetics; Germ cells; HSP70 Heat-Shock Proteins - metabolism; Male; Mammals; Meiosis; Mice; Mice, Knockout; Models, Biological; Molecular Sequence Data; Mutation; Pachytene stage; Proteins - metabolism; Retroelements - genetics; Retrotransposons; Ribonucleic acid; RNA; RNA Helicases - deficiency; RNA Helicases - genetics; RNA Helicases - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Seminiferous tubules; Sequence Homology, Amino Acid; Spermatocytes; Spermatocytes - metabolism; Spermatogenesis; Stem cells; Testes; Testis - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1007158107

Piwi-interacting RNAs (piRNAs) comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Here we show that the putative DExD-box helicase MOV10-like-1 (MOV10L1) is essential for silencing retrotransposons in the mouse male germline. Mov10l1 is specifically expressed in germ cells with increasing expression from gonocytes/type A spermatogonia to pachytene spermatocytes. Primary spermatocytes of Mov10l1 -/- mice show activation of LTR and LINE-1 retrotransposons, followed by cell death, causing male infertility and a complete block of spermatogenesis at early prophase of meiosis I. Despite the early expression of Mov10l1, germline stem cell maintenance appears unaffected in Mov10l1 -/- mice. MOV10L1 interacts with the Piwi proteins MILI and MIWI. MOV10L1 also interacts with heat shock 70-kDa protein 2 (HSPA2), a testis-enriched chaperone expressed in pachytene spermatocytes and also essential for male fertility. These studies reveal a crucial role of MOV10L1 in male fertility and piRNA-directed retrotransposon silencing in male germ cells and suggest that MOV10L1 functions as a key component of a safeguard mechanism for the genetic information in male germ cells of mammals.