Oh Nara, Kim Kyoung Mi, Cho Hana, Choe Junho, Kim Yoon Ki
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Biochem Biophys Res Commun. 2007 Oct 12;362(1):145-151. doi: 10.1016/j.bbrc.2007.07.169. Epub 2007 Aug 8.
The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons.
翻译起始的先驱轮次在新剪接的、与外显子连接复合体（EJC）结合的mRNA的翻译起始过程中发挥作用。核帽结合蛋白复合体CBP80/20在5'-端与那些mRNA结合，招募翻译起始复合体。作为翻译起始先驱轮次的结果，结合的EJCs从mRNA上解离，CBP80/20被细胞质帽结合蛋白eIF4E取代。由eIF4E指导的稳态翻译允许对生理条件的变化做出即时且快速的反应。在此，我们表明，无义介导的mRNA降解（NMD）仅局限于翻译起始的先驱轮次而非稳态翻译，即使在血清饥饿期间（此时稳态翻译被大幅消除）也能高效发生。相应地，CBP80保留在细胞核中，并且在血清饥饿条件下，加工小体的丰度和数量不受影响。这些结果表明，mRNA在血清饥饿期间进入翻译起始的先驱轮次，并且如果它们包含提前终止密码子，则会被靶向进行NMD。
