Abstract
RNA-binding proteins contribute to the formation of ribonucleoprotein (RNP) granules by phase transition, but regulatory mechanisms are not fully understood. Conserved fission yeast NDR (Nuclear Dbf2-Related) kinase Orb6 governs cell morphogenesis in part by spatially controlling Cdc42 GTPase. Here we describe a novel, independent function for Orb6 kinase in negatively regulating the recruitment of RNA-binding protein Sts5 into RNPs to promote polarized cell growth. We find that Orb6 kinase inhibits Sts5 recruitment into granules, its association with processing (P) bodies, and degradation of Sts5-bound mRNAs by promoting Sts5 interaction with 14-3-3 protein Rad24. Many Sts5-bound mRNAs encode essential factors for polarized cell growth, and Orb6 kinase spatially and temporally controls the extent of Sts5 granule formation. Disruption of this control system affects cell morphology and alters the pattern of polarized cell growth, revealing a role for Orb6 kinase in the spatial control of translational repression that enables normal cell morphogenesis.
Highlights
Many cellular processes, such as cell morphogenesis, migration, and asymmetric cell division, require eukaryotic cells to alter polarity and growth patterns (Lalli, 2014; Tahirovic and Bradke, 2009; Woodham and Machesky, 2014; Knoblich, 2008)
We describe a novel mechanism whereby NDR kinase Orb6 negatively regulates the recruitment of mRNA-binding protein Sts5 into ribonucleoprotein particles (RNPs) particles and Sts5 localization to P-bodies at least in part by promoting Sts5 interaction with 14-3-3 protein Rad24
By complementation screening of the orb6-as2 allele with mutants of other orb genes (Snell and Nurse, 1994; Verde et al, 1995), we found that sts5 mutants suppress the cell-separation defect associated with chemical inhibition of Orb6-as2 kinase (Figure 1A,d; Figure 1B; Verde et al, 1995) as compared to control cells (Figure 1A,c; Figure 1B). sts5 encodes an mRNA-binding protein with significant sequence homology to Ribonuclease II (RNB)–domain and Ribonuclease R–domain proteins (Toda et al, 1996; Jansen et al, 2009)
Summary
Many cellular processes, such as cell morphogenesis, migration, and asymmetric cell division, require eukaryotic cells to alter polarity and growth patterns (Lalli, 2014; Tahirovic and Bradke, 2009; Woodham and Machesky, 2014; Knoblich, 2008). Understanding the conserved mechanisms by which cells tune polarized cell growth has implications for studies of neuronal cell morphogenesis, neurodegenerative diseases, stem cell differentiation, and cancer (Yoshimura et al, 2006; Tahirovic and Bradke, 2009; Yamashita et al, 2010; Tanos and Rodriguez-Boulan, 2008). The fission yeast Schizosaccharomyces pombe is an excellent model system to study cell morphogenesis and growth because cells have a defined cylindrical shape that enables straightforward evaluation of changes in growth and polarity.
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