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Published on: June 27, 2013
Spatial control of translation repression and polarized growth by conserved NDR kinase Orb6 and RNA-binding protein
Illyce Nuñez1, Marbelys Rodriguez Pino1, David J Wiley1
1Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, United States.
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.
Insights
Fission yeast Orb6 kinase controls cell growth by regulating RNA-binding protein Sts5. Orb6 kinase limits Sts5 recruitment into RNP granules, enabling polarized cell growth and normal cell morphology.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- RNA-binding proteins form ribonucleoprotein (RNP) granules via phase transition.
- The fission yeast kinase Orb6 regulates cell morphogenesis by controlling Cdc42 GTPase.
- Mechanisms governing RNP granule formation and function are not fully elucidated.
Purpose of the Study:
- To investigate a novel function of Orb6 kinase in regulating RNA-binding proteins.
- To understand Orb6's role in the spatial control of RNP granule formation and polarized cell growth.
Main Methods:
- Utilized fission yeast as a model organism.
- Investigated the interaction between Orb6 kinase and RNA-binding protein Sts5.
- Analyzed the impact of Orb6 on Sts5 localization, RNP granule formation, and mRNA degradation.
Main Results:
- Orb6 kinase negatively regulates the recruitment of Sts5 into RNP granules and processing bodies.
- Orb6 promotes Sts5 interaction with the 14-3-3 protein Rad24, inhibiting Sts5 function.
- Orb6 kinase controls the spatial and temporal extent of Sts5 granule formation, affecting the degradation of Sts5-bound mRNAs.
- Disruption of Orb6-Sts5 regulation impairs cell morphology and polarized growth patterns.
Conclusions:
- Orb6 kinase plays a crucial role in negatively regulating Sts5 recruitment into RNP granules.
- This regulation by Orb6 is essential for promoting polarized cell growth and normal cell morphogenesis in fission yeast.
- Orb6 kinase mediates spatial control of translational repression through Sts5 granules, impacting cell growth and development.
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