FBF represses the Cip/Kip cell-cycle inhibitor CKI-2 to promote self-renewal of germline stem cells in C. elegans

Although the decision between stem cell self‐renewal and differentiation has been linked to cell‐cycle modifications, our understanding of cell‐cycle regulation in stem cells is very limited. Here, we report that FBF/Pumilio, a conserved RNA‐binding protein, promotes self‐renewal of germline stem cells by repressing CKI‐2Cip/Kip, a Cyclin E/Cdk2 inhibitor. We have previously shown that repression of CYE‐1 (Cyclin E) by another RNA‐binding protein, GLD‐1/Quaking, promotes germ cell differentiation. Together, these findings suggest that a post‐transcriptional regulatory circuit involving FBF and GLD‐1 controls the self‐renewal versus differentiation decision in the germline by promoting high CYE‐1/CDK‐2 activity in stem cells, and inhibiting CYE‐1/CDK‐2 activity in differentiating cells.