Landers Sharon M, Gallas Michelle R, Little Jaime, Long Roy M
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Eukaryot Cell. 2009 Jul;8(7):1072-83. doi: 10.1128/EC.00084-09. Epub 2009 May 8.
Intracellular and intercellular polarity requires that specific proteins be sorted to discreet locations within and between cells. One mechanism for sorting proteins is through RNA localization. In Saccharomyces cerevisiae, ASH1 mRNA localizes to the distal tip of the bud, resulting in the asymmetric sorting of the transcriptional repressor Ash1p. ASH1 mRNA localization requires four cis-acting localization elements and the trans-acting factors Myo4p, She3p, and She2p. Myo4p is a type V myosin motor that functions to directly transport ASH1 mRNA to the bud. She2p is an RNA-binding protein that directly interacts with the ASH1 mRNA cis-acting elements. Currently, the role for She3p in ASH1 mRNA localization is as an adaptor protein, since it can simultaneously associate with Myo4p and She2p. Here, we present data for two novel mutants of She3p, S348E and the double mutant S343E S361E, that are defective for ASH1 mRNA localization, and yet both of these mutants retain the ability to associate with Myo4p and She2p. These observations suggest that She3p possesses a novel activity required for ASH1 mRNA localization, and our data imply that this function is related to the ability of She3p to associate with ASH1 mRNA. Interestingly, we determined that She3p is phosphorylated, and global mass spectrometry approaches have determined that Ser 343, 348, and 361 are sites of phosphorylation, suggesting that the novel function for She3p could be negatively regulated by phosphorylation. The present study reveals that the current accepted model for ASH1 mRNA localization does not fully account for the function of She3p in ASH1 mRNA localization.
细胞内和细胞间的极性要求特定蛋白质被分选到细胞内和细胞间的特定位置。蛋白质分选的一种机制是通过RNA定位。在酿酒酵母中,ASH1 mRNA定位于芽的远端,导致转录抑制因子Ash1p的不对称分选。ASH1 mRNA定位需要四个顺式作用定位元件以及反式作用因子Myo4p、She3p和She2p。Myo4p是一种V型肌球蛋白马达,其功能是直接将ASH1 mRNA转运到芽中。She2p是一种RNA结合蛋白,它直接与ASH1 mRNA顺式作用元件相互作用。目前,She3p在ASH1 mRNA定位中的作用是作为衔接蛋白,因为它可以同时与Myo4p和She2p结合。在这里,我们展示了She3p的两个新突变体S348E和双突变体S343E S361E的数据,它们在ASH1 mRNA定位方面存在缺陷,但这两个突变体都保留了与Myo4p和She2p结合的能力。这些观察结果表明,She3p具有ASH1 mRNA定位所需的新活性,我们的数据表明该功能与She3p与ASH1 mRNA结合的能力有关。有趣的是,我们确定She3p被磷酸化,全局质谱方法已确定Ser 343、348和361是磷酸化位点,这表明She3p的新功能可能受到磷酸化的负调控。本研究表明,目前被接受的ASH1 mRNA定位模型不能完全解释She3p在ASH1 mRNA定位中的功能。