title: Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development.
abstract: RNA-binding proteins (RBPs) play important roles for generating various cell types in many developmental processes, including eggs and sperms. Nanos is widely known as an evolutionarily conserved RNA-binding protein implicated in germ cell development. Mouse NANOS2 interacts directly with the CCR4-NOT (CNOT) deadenylase complex, resulting in the suppression of specific RNAs. However, the mechanisms involved in target specificity remain elusive. We show that another RBP, Dead end1 (DND1), directly interacts with NANOS2 to load unique RNAs into the CNOT complex. This interaction is mediated by the zinc finger domain of NANOS2, which is essential for its association with target RNAs. In addition, the conditional deletion of DND1 causes the disruption of male germ cell differentiation similar to that observed in Nanos2-KO mice. Thus, DND1 is an essential partner for NANOS2 that leads to the degradation of specific RNAs. We also present the first evidence that the zinc finger domain of Nanos acts as a protein-interacting domain for another RBP, providing a novel insight into Nanos-mediated germ cell development.
authors.affiliation: Division of Materials Science and Chemical Engineering, Faculty of Engineering, Yokohama National University, Yokohama Kanagawa, Japan atsuzuki@ynu.ac.jp ysaga@lab.nig.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Division of Materials Science and Chemical Engineering, Graduate School of Engineering Yokohama National University, Yokohama Kanagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Niimi
authors.affiliation: Mass Spectrometric Unit, RIKEN Center for Developmental Biology, Kobe Hyogo, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinmyozu
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Mishima Shizuoka, Japan.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Mishima Shizuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Mishima Shizuoka, Japan atsuzuki@ynu.ac.jp ysaga@lab.nig.ac.jp.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D000066473:Embryonic Germ Cells / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000502:physiology; D016335:Zinc Fingers / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C500862:Dnd1 protein, mouse; C477341:Nanos2 protein, mouse; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D012313:RNA
keywords: Dead end; Nanos; RNA; germ cell