Phosphorylation of the RNA-binding protein Zfs1 modulates sexual differentiation in fission yeast.

Francisco J Navarro,Paul Nurse,Probir Chakravarty

doi:10.1242/jcs.208066

Abstract

ABSTRACTSexual differentiation in the fission yeast Schizosaccharomyces pombe promotes cell cycle arrest and extensive changes in gene expression, resulting in cell-to-cell fusion, the exchange of hereditary material and specialized cell division. These events are detrimental to the cell if they are triggered in inappropriate conditions, and therefore the decision to differentiate must be precisely controlled. Here, we investigated the role of the RNA-binding protein Zfs1 in this process by identifying its targets and characterizing novel post-translational regulatory mechanisms. We found that Zfs1 negatively regulates the G1 cyclin Puc1, and deregulated Puc1 levels inhibit differentiation in the zfs1Δ mutant. We also found that Zfs1 undergoes phosphorylation, which is stimulated upon nitrogen depletion or inhibition of the TOR pathway. Phosphorylation of Zfs1 modulates accumulation of Puc1 and plays an important role in the response of the cell to sexual differentiation signals. We propose that Zfs1 functions as an integrator of nutrient information to modulate sexual differentiation, contributing to the establishment of the differentiation-activating threshold.

Highlights

Eukaryotic cells initiate different developmental fates in G1 phase in response to various signals including nutrient availability, growth factors and differentiation stimuli
AREs are normally located in the 3′untranslated regions (UTRs) of CCCH-type tandem zinc-finger RNAbinding proteins (RBPs) targets, we found that this motif was frequent in the 5′UTR of the IP-enriched genes and in the Zfs1 RNA target group (Fig. 1C), suggesting that Zfs1 is restricted to binding AREs located in the 3′UTR and binds those in the 5′ UTR
The Zfs1-6A mutant had lower amounts of the Puc1 protein than the wild type (WT) strain mRNA levels were unchanged (Fig. 6), suggesting that Zfs1 may have a function in mRNA translation or protein turnover

Summary

Introduction

Eukaryotic cells initiate different developmental fates in G1 phase in response to various signals including nutrient availability, growth factors and differentiation stimuli. These signals determine, for example, whether cells enter a mitotic cycle, a quiescent state, or undergo cell differentiation. Yeast haploid cells of different mating types arrest in the G1 phase of the cell cycle and undergo a genetic programme involving hundreds of genes that eventually leads to cell conjugation and the formation of a diploid zygote. In the fission yeast Schizosaccharomyces pombe, sexual differentiation is triggered by nitrogen depletion and by the exchange of pheromones between cells of different mating types (Nielsen, 2004; Yamamoto, 2004).

Methods

Results

Conclusion