Ma Xiaoju Max, Yoon Sang-Oh, Richardson Celeste J, Jülich Kristina, Blenis John
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell. 2008 Apr 18;133(2):303-13. doi: 10.1016/j.cell.2008.02.031.
Different protein complexes form on newly spliced mRNA to ensure the accuracy and efficiency of eukaryotic gene expression. For example, the exon junction complex (EJC) plays an important role in mRNA surveillance. The EJC also influences the first, or pioneer round of protein synthesis through a mechanism that is poorly understood. We show that the nutrient-, stress-, and energy-sensing checkpoint kinase, mTOR, contributes to the observed enhanced translation efficiency of spliced over nonspliced mRNAs. We demonstrate that, when activated, S6K1 is recruited to the newly synthesized mRNA by SKAR, which is deposited at the EJC during splicing, and that SKAR and S6K1 increase the translation efficiency of spliced mRNA. Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis.
不同的蛋白质复合物在新剪接的mRNA上形成，以确保真核基因表达的准确性和效率。例如，外显子连接复合物（EJC）在mRNA监测中起重要作用。EJC还通过一种尚不清楚的机制影响第一轮或先驱轮蛋白质合成。我们发现，营养、应激和能量感应检查点激酶mTOR有助于观察到的剪接mRNA比未剪接mRNA翻译效率的提高。我们证明，激活时，S6K1通过SKAR被招募到新合成的mRNA上，SKAR在剪接过程中沉积在EJC处，并且SKAR和S6K1提高了剪接mRNA的翻译效率。因此，当细胞处于支持蛋白质合成的条件下时，SKAR介导的激活的S6K1向新加工的mRNA颗粒的募集充当了mTOR检查点信号与先驱轮翻译之间的管道。
