Antagonistic control of Caenorhabditis elegans germline stem cell proliferation and differentiation by PUF proteins FBF-1 and FBF-2.

Xiaobo Wang,Mary Ellenbecker,Ekaterina Voronina,Emily Osterli,Benjamin Hickey,Nicholas J Day,Mikaya Terzo

doi:10.7554/elife.52788

Abstract

Stem cells support tissue maintenance, but the mechanisms that coordinate the rate of stem cell self-renewal with differentiation at a population level remain uncharacterized. We find that two PUF family RNA-binding proteins FBF-1 and FBF-2 have opposite effects on Caenorhabditis elegans germline stem cell dynamics: FBF-1 restricts the rate of meiotic entry, while FBF-2 promotes both cell division and meiotic entry rates. Antagonistic effects of FBFs are mediated by their distinct activities toward the shared set of target mRNAs, where FBF-1-mediated post-transcriptional control requires the activity of CCR4-NOT deadenylase, while FBF-2 is deadenylase-independent and might protect the targets from deadenylation. These regulatory differences depend on protein sequences outside of the conserved PUF family RNA-binding domain. We propose that the opposing FBF-1 and FBF-2 activities serve to modulate stem cell division rate simultaneously with the rate of meiotic entry.

Highlights

Adult tissue maintenance relies on the activity of stem cells that self-renew and produce differentiating progeny in step with tissue demands (Morrison and Kimble 2006)
We found that the stem and progenitor cell (SPC) zone size maintained by GFP::FBF-2(vrm) (Figure 6Bv) is significantly larger than that maintained by GFP::FBF-2(wt) (Figure 6Biv) and the endogenous FBF-2 (Figure 6Bii) and significantly shorter than that maintained by FBF-1
We found that SPC zone size of fbf-1(lf) fbf-2(lf); gfp::fbf385 2(vrm) after RNAi of CCR4-NOT subunits becomes significantly shorter than the control

Summary

Introduction

Adult tissue maintenance relies on the activity of stem cells that self-renew and produce differentiating progeny in step with tissue demands (Morrison and Kimble 2006). 62 Analysis of C. elegans germline stem cell maintenance identified a number of genes affecting SPC self-renewal and differentiation (Hansen and Schedl 2013).Genes essential for self-renewal include GLP-1/Notch and two highly similar Pumilio and FBF (PUF) family RNA-binding proteins called FBF-1 and FBF-2 (Austin and Kimble 1987; Crittenden and others 2002; Zhang and others 1997). We sought to take advantage of the distinct SPC numbers maintained by individual FBF proteins to understand how they regulate the dynamics of SPCs proliferation and differentiation and probe the functional differences between FBFs. 120 Elaborating on the general contribution of PUF proteins to stem cell maintenance, we describe here that FBF-1 and FBF-2 have opposing effects on the rate of germline SPCs proliferation and the rate of meiotic entry. The dual regulation of SPC self-renewal and differentiation by FBFs effectively allows the stem cells to match cell division rate with the demand for meiotic cell output

Results

Discussion

Conclusion