Regulation of gene expression via translational buffering

Translation of an mRNA represents a critical step during the expression of protein-coding genes. As mechanisms governing post-transcriptional regulation of gene expression are progressively unveiled, it is becoming apparent that transcriptional programs are not fully reflected in the proteome. Herein, we highlight a previously under-appreciated post-transcriptional mode of regulation of gene expression termed translational buffering. In principle, translational buffering opposes the impact of alterations in mRNA levels on the proteome. We further describe three types of translational buffering: compensation, which maintains protein levels e.g. across species or individuals; equilibration, which retains pathway stoichiometry; and offsetting, which acts as a reversible mechanism that maintains the levels of selected subsets of proteins constant despite genetic alteration and/or stress-induced changes in corresponding mRNA levels. While mechanisms underlying compensation and equilibration have been reviewed elsewhere, the principal focus of this review is on the less-well understood mechanism of translational offsetting. Finally, we discuss potential roles of translational buffering in homeostasis and disease.

Automated summary

Translation of mRNA is a critical step in protein-coding gene expression, and translational buffering plays an important role in regulating gene expression post-transcriptionally. There are three types of translational buffering: compensation, equilibration, and offsetting, each serving to maintain protein levels despite changes in mRNA levels. This mechanism, particularly translational offsetting, is less well understood but may have significant implications in maintaining protein homeostasis and in disease states.