Zhang Xingqian, Gao Xiangwei, Coots Ryan Alex, Conn Crystal S, Liu Botao, Qian Shu-Bing
Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
1] Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [2] Graduate Field of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
Nat Struct Mol Biol. 2015 May;22(5):404-10. doi: 10.1038/nsmb.3010. Epub 2015 Apr 13.
In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although decades have passed since the first description of the heat-shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report an unexpected role for mitochondrial ribosomal protein L18 (MRPL18) in the mammalian cytosolic stress response. MRPL18 bears a downstream CUG start codon and generates a cytosolic isoform in a stress-dependent manner. Cytosolic MRPL18 incorporates into the 80S ribosome and facilitates ribosome engagement on mRNAs selected for translation during stress. MRPL18 knockdown has minimal effects on mitochondrial function but substantially dampens cytosolic HSP expression at the level of translation. Our results uncover a hitherto-uncharacterized stress-adaptation mechanism in mammalian cells, which involves formation of a 'hybrid' ribosome responsible for translational regulation during the cytosolic stress response.
作为对压力的响应，细胞会减弱整体蛋白质合成，但允许编码热休克蛋白（HSPs）的mRNA进行高效翻译。尽管自首次描述热休克反应以来已经过去了几十年，但细胞如何实现对HSP合成的翻译控制仍然是个谜。在这里，我们报告了线粒体核糖体蛋白L18（MRPL18）在哺乳动物细胞质应激反应中的一个意想不到的作用。MRPL18带有一个下游CUG起始密码子，并以应激依赖的方式产生一种细胞质异构体。细胞质中的MRPL18整合到80S核糖体中，并促进核糖体与应激期间被选择用于翻译的mRNA结合。敲低MRPL18对线粒体功能影响极小，但在翻译水平上显著抑制细胞质HSP的表达。我们的结果揭示了哺乳动物细胞中一种迄今未被描述的应激适应机制，该机制涉及形成一种“混合”核糖体，负责细胞质应激反应期间的翻译调控。
