Ribosome Collisions Result in +1 Frameshifting in the Absence of No-Go Decay

Abstract

SUMMARYDuring 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.