title: Interaction between NANOS2 and the CCR4-NOT deadenylation complex is essential for male germ cell development in mouse.
abstract: Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs) of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10) fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s) that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex.
authors.affiliation: Interdisciplinary Research Center, Yokohama National University, Yokohama, Kanagawa, Japan. atsuzuki@ynu.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.forename: Kei
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Morita
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000254:growth & development* / Q000378:metabolism*; D013737:Testis / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C528690:CNOT1 protein, human; D002352:Carrier Proteins; C477341:Nanos2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D012260:Ribonucleases; C445084:mRNA deadenylase