A Cooperative Mechanism of Target RNA Selection via Germ Cell-Specific RNA-Binding Proteins, NANOS2 and DND1

Abstract

The germ cell-specific RNA-binding protein, NANOS2, plays a pivotal role in male gonocyte differentiation and spermatogonial stem cell maintenance. Although NANOS2 interacts with the CNOT deadenylation complex and Dead end 1 (DND1) to repress target RNAs, the molecular mechanisms underlying target mRNA selection remain unclear because of the limited cell resource in vivo. We succeeded in reproducing the NANOS2-DND1 function in somatic cells. Using this system, we found that NANOS2 recruits the CNOT complex to the mRNAs that are recognized and bound by DND1 through its own RNA-binding domain. In addition, by analyzing gonocytes expressing domain-swapped NANOS2 with the NANOS2-zinc finger (ZnF) domain substituted by the DND1-RNA recognition motifs (RRMs), we found that the NANOS2-ZnF domain is required for target mRNA selection and DND1 interaction. This study unveiled the mechanisms of the target RNA recognition underlying the partnership of two RNA-binding proteins, which leads to male germ cell development.