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.
| Original language | English |
|---|---|
| Article number | e52788 |
| Pages (from-to) | 1-36 |
| Number of pages | 36 |
| Journal | eLife |
| Volume | 9 |
| DOIs | |
| State | Published - Aug 2020 |
Funding
We thank the members of Voronina laboratory for insightful discussions and Geraldine Seydoux for comments on our manuscript. We are grateful to Ella Baumgarten and Jessica Bailey for help with cloning and crosses. We appreciate Ariz Mohammad for sharing the modified R script (originally from the Kimble lab) and instructions on using R for cell counts. Some nematode strains used in this study were provided by the Caenorhabditis Genetics Center funded by the NIH (P40OD010440). Confocal microscopy was performed in the University of Montana BioSpectroscopy Core Research Laboratory operated with support from NIH awards P20GM103546 and S10OD021806. This work was supported by the NIH grants GM109053 to EV and P20GM103546 (S Sprang, PI; EV Pilot Project PI), American Heart Association Fellowship 18PRE34070028 to XW, and Montana Academy of Sciences award to XW. We thank the members of Voronina laboratory for insightful discussions and Geraldine Seydoux for comments on our manuscript. We are grateful to Ella Baumgarten and Jessica Bailey for help with cloning and crosses. We appreciate Ariz Mohammad for sharing the modified R script (originally from the Kimble lab) and instructions on using R for cell counts. Some nematode strains used in this study were provided by the Caenorhabditis Genetics Center funded by the NIH (P40OD010440). Confocal microscopy was performed in the University of Montana BioSpectroscopy Core Research Laboratory operated with support from NIH awards P20GM103546 and S10OD021806. This work was supported by the NIH grants GM109053 to EV and P20GM103546 (S Sprang, PI; EV Pilot Proj-ect PI), American Heart Association Fellowship 18PRE34070028 to XW, and Montana Academy of Sciences award to XW.
| Funders | Funder number |
|---|---|
| GM109053, S10OD021806, P40OD010440 | |
| P20GM103546 | |
| American Heart Association | 18PRE34070028 |