Nuñez Illyce, Rodriguez Pino Marbelys, Wiley David J, Das Maitreyi E, Chen Chuan, Goshima Tetsuya, Kume Kazunori, Hirata Dai, Toda Takashi, Verde Fulvia
Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, United States.
Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, United States.
Elife. 2016 Jul 30;5:e14216. doi: 10.7554/eLife.14216.
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.
RNA结合蛋白通过相变促进核糖核蛋白（RNP）颗粒的形成，但其调控机制尚未完全明确。保守的粟酒裂殖酵母NDR（核Dbf2相关）激酶Orb6部分通过空间控制Cdc42 GTP酶来调控细胞形态发生。在此，我们描述了Orb6激酶的一种新的独立功能，即负向调节RNA结合蛋白Sts5募集到RNP中以促进细胞极性生长。我们发现，Orb6激酶通过促进Sts5与14-3-3蛋白Rad24相互作用，抑制Sts5募集到颗粒中、其与加工（P）小体的结合以及Sts5结合的mRNA的降解。许多Sts5结合的mRNA编码细胞极性生长的必需因子，并且Orb6激酶在空间和时间上控制Sts5颗粒形成的程度。该控制系统的破坏会影响细胞形态并改变细胞极性生长模式，揭示了Orb6激酶在翻译抑制的空间控制中发挥作用，从而实现正常的细胞形态发生。
