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

Elife. 2020 Aug 17:9:e52788. 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.

Keywords: C. elegans; CCR4-NOT; PUF; cell cycle; deadenylase; developmental biology; germline; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation / genetics*
  • Cell Self Renewal / genetics*
  • Germ Cells / cytology
  • Larva / genetics
  • Larva / growth & development
  • Larva / physiology
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Stem Cells / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • RNA-Binding Proteins
  • fem-3-binding protein, C elegans