Messenger RNA

Translation (biology)

Ribosome profiling

Biology

Gene

Genetic code

Paleontology

Context (archaeology)

Computational biology

Cell biology

Protein biosynthesis

Amino acid

Genetics

Biochemistry

EF-Tu

Ribosome

Nature Reviews Molecular Cell Biology

During protein synthesis, ribosomes encounter many roadblocks, the outcomes of which are largely determined by substrate availability, amino acid features and reaction kinetics. Prolonged ribosome stalling is likely to be resolved by ribosome rescue or quality control pathways, whereas shorter stalling is likely to be resolved by ongoing productive translation. How ribosome function is affected by such hindrances can therefore have a profound impact on the translational output (yield) of a particular mRNA. In this Review, we focus on these roadblocks and the resumption of normal translation elongation rather than on alternative fates wherein the stalled ribosome triggers degradation of the mRNA and the incomplete protein product. We discuss the fundamental stages of the translation process in eukaryotes, from elongation through ribosome recycling, with particular attention to recent discoveries of the complexity of the genetic code and regulatory elements that control gene expression, including ribosome stalling during elongation, the role of mRNA context in translation termination and mechanisms of ribosome rescue that resemble recycling. Ribosomes encounter obstacles during translation elongation that cause their stalling and can have a profound impact on protein yield. Ribosome stalling depends on the genetic code, amino acid availability, regulatory elements and mRNA context and can be resolved by resumption of translation or by ribosome rescue and recycling.

Roadblocks and resolutions in eukaryotic translation