Tale of NANOS
Yumiko Saga (National Institute of Genetics)
During germ cell development, RNA regulation mediated by several RNA binding proteins (RBPs) plays crucial roles. Nanos is one of most famous RNA binding proteins, but it was originally identified as a posterior determinant in Drosophila in 1980’s and it was re-discovered as an essential factor for germ cell development after 1996. Since then, the importance of Nanos homologue in germ cells has been documented from many species. My germ cell research was also started by searching for Nanos homologue in mice. For more than 20 years, I have been trying to elucidate molecular functions of mouse Nanos homologues, NANOS2 and NANOS3. Our group found that NANOS proteins interact with CCR4-NOT complexes and a partner protein, DEAD END1, to trap and recruit target RNAs (such as Dazl, Sohlh2) to P-bodies for the repression (ref1, 2). However, many important questions remain unanswered: 1) What is the most critical target mRNA responsible for germ cell development; 2) How target RNAs are recognized and selected; 3) How P-bodies are formed and their dynamism regulated. In this seminar, I would like to summarize previous findings and up-date the information including our current findings. I also would like to introduce AID-mediated protein knockdown mouse systems (ref3) to facilitate functional analysis in vivo if I have the time.
1.Suzuki A, Igarashi K, Aisaki K, Kanno J, Saga Y. NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs. Proc Natl Acad Sci U S A. ;107(8):3594-9, 2010
2.Suzuki A, Niimi Y, Shinmyozu K, Zhou Z, Kiso M, Saga Y. Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development. EMBO Rep. 2016 Jan;17(1):37-46. doi: 10.15252/embr.201540828. Epub 2015 Nov 20
3.Yesbolatova A, Saito Y, Kitamoto N, Makino-Itou H, Ajima R, Nakano R, Nakaoka H, Fukui K, Gamo K, Tominari Y, Takeuchi H, Saga Y, Hayashi KI, Kanemaki MT. The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice. Nat Commun. 2020 Nov 11;11(1):5701. doi: 10.1038/s41467-020-19532-z.
