title: MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Robert J A
authors.initials: RJ
authors.lastname: Frost
authors.forename: F Kent
authors.initials: FK
authors.lastname: Hamra
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qi
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D005298:Fertility; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000378:metabolism; D020365:RNA Helicases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism*; D018626:Retroelements / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; C490434:Hspa2 protein, mouse; C448522:Piwil1 protein, mouse; C448521:Piwil2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D018626:Retroelements; C477006:Mov10l1 protein, mouse; D020365:RNA Helicases