A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly.
A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly.
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DOI：
10.1038/ncb1783
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发表时间：
2008-10
影响因子：
21.3
通讯作者：
Anderson, Paul
中科院分区：
文献类型：
--
作者：
Ohn, Takbum;Kedersha, Nancy;Hickman, Tyler;Tisdale, Sarah;Anderson, Paul
应激颗粒（SG）和加工体（PB）是显微镜下可见的核糖核蛋白颗粒，它们共同调节信使RNA的翻译和降解。使用RNA介导的干扰为基础的屏幕，我们确定了101个人类基因所需的SG大会，39个基因所需的PB大会，和31个基因所需的协调SG和PB大会。虽然51个基因编码的蛋白质参与mRNA的翻译，剪接和转录，大多数没有明显的RNA代谢。我们发现，几个组件的己糖胺生物合成途径，可逆地修改蛋白质与O-连接的N-乙酰葡糖胺（O-GlcNAc）在应对压力，需要SG和PB组装。O-GlcNAc修饰的蛋白质是SG而不是PB的主要组分，并且包括RACK 1（活化C激酶1的受体）、抑制素-2、甘油醛-3-磷酸脱氢酶和许多核糖体蛋白。我们的研究结果表明，O-GlcNAc修饰的翻译机器是必需的聚集成SG的非翻译信使核糖核蛋白。芽殖酵母中缺乏己糖胺生物合成途径的酶可能导致哺乳动物SG和相关酵母EGP（含有eIF 4 E、4G和Pab 1）体之间的差异。
Stress granules (SGs) and processing bodies (PBs) are microscopically visible ribonucleoprotein granules that cooperatively regulate the translation and decay of messenger RNA. Using an RNA-mediated interference-based screen, we identify 101 human genes required for SG assembly, 39 genes required for PB assembly, and 31 genes required for coordinate SG and PB assembly. Although 51 genes encode proteins involved in mRNA translation, splicing and transcription, most are not obviously associated with RNA metabolism. We find that several components of the hexosamine biosynthetic pathway, which reversibly modifies proteins with O-linked N-acetylglucosamine (O-GlcNAc) in response to stress, are required for SG and PB assembly. O-GlcNAc-modified proteins are prominent components of SGs but not PBs, and include RACK1 (receptor for activated C kinase 1), prohibitin-2, glyceraldehyde-3-phosphate dehydrogenase and numerous ribosomal proteins. Our results suggest that O-GlcNAc modification of the translational machinery is required for aggregation of untranslated messenger ribonucleoproteins into SGs. The lack of enzymes of the hexosamine biosynthetic pathway in budding yeast may contribute to differences between mammalian SGs and related yeast EGP (eIF4E, 4G and Pab1 containing) bodies.
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