title: Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile.
abstract: Piwi proteins and their associated Piwi-interacting RNAs (piRNAs) are implicated in transposon silencing in the mouse germ line. There is currently little information on additional proteins in the murine Piwi complex and how they might regulate the entry of transcripts that accumulate as piRNAs in the Piwi ribonucleoprotein (piRNP). We isolated Mili-containing complexes from adult mouse testes and identified Tudor domain-containing protein-1 (Tdrd1) as a factor specifically associated with the Mili piRNP throughout spermatogenesis. Complex formation is promoted by the recognition of symmetrically dimethylated arginines at the N terminus of Mili by the tudor domains of Tdrd1. Similar to a Mili mutant, mice lacking Tdrd1 show derepression of L1 transposons accompanied by a loss of DNA methylation at their regulatory elements and delocalization of Miwi2 from the nucleus to the cytoplasm. Finally, we show that Mili piRNPs devoid of Tdrd1 accept the entry of abundant cellular transcripts into the piRNA pathway and accumulate piRNAs with a profile that is drastically different from that of the wild type. Our data suggest that Tdrd1 ensures the entry of correct transcripts into the normal piRNA pool.
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Reuter
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Chuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Pillai
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D060565:Argonaute Proteins; D018797:Cell Cycle Proteins; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics*; D008297:Male; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000172:deficiency* / Q000502:physiology; D013091:Spermatogenesis; D013737:Testis / Q000737:chemistry
chemical_list: D060565:Argonaute Proteins; D018797:Cell Cycle Proteins; D004251:DNA Transposable Elements; D046912:Multiprotein Complexes; C448521:Piwil2 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017411:Ribonucleoproteins, Small Nuclear; C488681:Tdrd1 protein, mouse