Interpreting ribosome dynamics during mRNA translation.

Translation takes a central position in gene expression, and its swift response to environmental stress is evolutionarily conserved. Upon chemical damage to the messenger RNA (mRNA) or the lack of building blocks, the ribosome stalls during elongation and halts the production line. Even under normal growth conditions, the translation machinery encounters constant hindrances such as varied codon composition or nascent chains with distinct features. However, it is challenging to define these kinetics experimentally, partly due to the inherent variations of ribosome behavior during mRNA translation. To ensure the flow of ribosomal traffic, cells employ several mechanisms to circumvent the traffic jam. When the roadblock is not resolved timely, trailing ribosomes can collide with stalled ribosomes. However, the boundary between physiological queuing and pathological collision is often blurred, representing a fundamental gap in our understanding of ribosome dynamics. To cope with translational barriers, several signaling pathways are activated to adjust the rate of global translation and rescue the local stalled ribosome. Deficiencies in cellular response to translational stress have been associated with a wide array of human diseases. In this review, we focus on fundamental aspects of the ribosome dynamics during mRNA translation. We provide an overview of causes, outcomes, and cellular responses to ribosome stalling and collision on mRNA. We highlight questions that may clarify the biological roles of distinct ribosome behavior during mRNA translation and emphasize the mechanistic connection between altered ribosome dynamics and human diseases.