PUF family proteins FBF-1 and FBF-2 regulate germline stem and progenitor cell proliferation and differentiation in C. elegans

Wang X, Ellenbecker M, Hickey B, Day NJ, Voronina E.
Preprint from
31 October 2019


Stem cells support tissue maintenance, but the mechanisms that balance the rate of stem cell self-renewal with differentiation at a population level remain uncharacterized. Through investigating the regulation of germline stem cells by two PUF family RNA-binding proteins FBF-1 and FBF-2 in C. elegans , we find that FBF-1 restricts differentiation, while FBF-2 promotes both proliferation and differentiation. FBFs act on a shared set of target mRNAs; however, FBF-1 destabilizes target transcripts, while FBF-2 promotes their accumulation. These regulatory differences result in complementary effects of FBFs on stem cells. We identify a mitotic cyclin as one of the targets affecting stem cell homeostasis. FBF-1-mediated translational control requires the activity of CCR4-NOT deadenylase. Distinct abilities of FBFs to cooperate with CCR4-NOT depend on protein sequences outside of the conserved PUF family RNA-binding domain. We propose that the combination of FBF activities regulates the dynamics of germline stem cell proliferation and differentiation.