Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development. (20th November 2015)

• Record Type: Journal Article
• Authors: Suzuki, Atsushi; Niimi, Yuki; Shinmyozu, Kaori; Zhou, Zhi; Kiso, Makoto; Saga, Yumiko
• Is Part Of: EMBO reports. Volume 17:Number 1(2016:Jan.)
• Page Start: 37
• Page End: 46
• Publication Date: 2015-11-20
• Subjects: Dead end -- germ cell -- Nanos -- RNA; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201540828
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: The NANOS2–Dead end1 (DND1) complex is required for the differentiation of mouse male germ cells. DND1 associates with the CCR4–NOT deadenylase complex via NANOS2, and promotes the degradation of specific NANOS2‐associated mRNAs. Mouse NANOS2 directly interacts with DND1. DND1 co‐localizes with NANOS2 in P‐bodies of male embryonic germ cells. DND1 is essential for NANOS2 binding to certain target RNAs. Abstract : The NANOS2–Dead end1 (DND1) complex is required for the differentiation of mouse male germ cells. DND1 associates with the CCR4–NOT deadenylase complex via NANOS2 and promotes the degradation of specific NANOS2‐associated mRNAs.