RRC ID 67366
Author Wright D, Kiso M, Saga Y.
Title Genetic and structural analysis of the in vivo functional redundancy between murine NANOS2 and NANOS3.
Journal Development
Abstract NANOS2 and NANOS3 are evolutionarily conserved RNA-binding proteins involved in murine germ cell development. NANOS3 is required for protection from apoptosis during migration and gonadal colonization in both sexes, whereas NANOS2 is male-specific and required for the male-type differentiation of germ cells. Ectopic NANOS2 rescues the functions of NANOS3, but NANOS3 cannot rescue NANOS2 function, even though its expression is upregulated in Nanos2-null conditions. It is unknown why NANOS3 cannot rescue NANOS2 function and it is unclear whether NANOS3 plays any role in male germ cell differentiation. To address these questions, we made conditional Nanos3/Nanos2 knockout mice and chimeric mice expressing chimeric NANOS proteins. Conditional double knockout of Nanos2 and Nanos3 led to the rapid loss of germ cells, and in vivo and in vitro experiments revealed that DND1 and NANOS2 binding is dependent on the specific NANOS2 zinc-finger structure. Moreover, murine NANOS3 failed to bind CNOT1, an interactor of NANOS2 at its N-terminal. Collectively, our study suggests that the inability of NANOS3 to rescue NANOS2 function is due to poor DND1 recruitment and CNOT1 binding.
Volume 148(1)
Published 2021-1-11
DOI 10.1242/dev.191916
PII dev.191916
PMID 33199444
MeSH Amino Acid Sequence Animals Apoptosis Cytoprotection Male Mice, Knockout Neoplasm Proteins / metabolism Protein Domains RNA-Binding Proteins / chemistry* RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Recombinant Proteins / metabolism Sex Differentiation / genetics Spermatozoa / metabolism Structure-Activity Relationship Zinc Fingers
IF 5.611
DNA material Nanos2-cKO vector (RDB18643) Nanos3-cKO vector (RDB18644)