Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada.
Cell Metab. 2013 Mar 5;17(3):386-98. doi: 10.1016/j.cmet.2013.02.006.
RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.
RNA 结合蛋白是转录后基因调控的核心，协调细胞 RNA 的加工、储存和处理。我们在这里表明，先前涉及流感 mRNA 结合和选择性翻译的 GRSF1 被靶向到线粒体，在那里它形成颗粒，与线粒体核仁旁边新合成的 mtRNA 的焦点共定位。GRSF1 优先结合从 mtDNA 轻链上三个连续基因转录的 RNA，即 ND6 mRNA 和 cytb 和 ND5 的长非编码 RNA，每个基因都包含多个共识结合序列。RNAi 介导的 GRSF1 敲低导致线粒体 RNA 稳定性改变、mRNA 和 lncRNA 异常加载到线粒体核糖体上以及核糖体组装受损。这导致特定的蛋白质合成缺陷和无法组装正常数量的氧化磷酸化复合物。这些数据表明 GRSF1 是转录后线粒体基因表达的关键调节剂。
