Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Cell Rep. 2019 Aug 13;28(7):1679-1689.e4. doi: 10.1016/j.celrep.2019.07.046.
During translation, an mRNA is typically occupied by multiple ribosomes sparsely distributed across the coding sequence. This distribution, mediated by slow rates of initiation relative to elongation, ensures that they rarely collide with each other, but given the stochastic nature of protein synthesis, collision events do occur. Recent work from our lab suggested that collisions signal for mRNA degradation through no-go decay (NGD). We have explored the impact of stalling on ribosome function when NGD is compromised and found it to result in +1 frameshifting. We used reporters that limit the number of ribosomes on a transcript to show that +1 frameshifting is induced through ribosome collision in yeast and bacteria. Furthermore, we observe a positive correlation between ribosome density and frameshifting efficiency. It is thus tempting to speculate that NGD, in addition to its role in mRNA quality control, evolved to cope with stochastic collision events to prevent deleterious frameshifting events.
在翻译过程中，mRNA 通常被多个核糖体占据，这些核糖体在编码序列中稀疏分布。这种分布是由起始相对于延伸的缓慢速度介导的，确保它们很少相互碰撞，但考虑到蛋白质合成的随机性，碰撞事件确实会发生。我们实验室的最近研究表明，碰撞通过无终止衰变（NGD）发出 mRNA 降解的信号。我们研究了当 NGD 受到干扰时对核糖体功能的影响，发现它会导致+1 移码。我们使用限制转录本上核糖体数量的报告基因，证明在酵母和细菌中，核糖体碰撞会诱导+1 移码。此外，我们观察到核糖体密度与移码效率之间存在正相关。因此，人们不禁推测，NGD 除了在 mRNA 质量控制中发挥作用外，还进化到可以应对随机碰撞事件，以防止有害的移码事件。
