Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1869, Issue 1, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2021.119140
Keywords
mRNA translation; Translational buffering; Translational offsetting; Posttranscriptional regulation; tRNA epitranscriptomics
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia [APP1141339]
- Victorian Cancer Agency Early Career Research Fellowship [ECRF20018]
- University of Melbourne's Melbourne International Research Scholarship (MIRS)
- Canadian Institutes of Health Research (CIHR) [MOP-363027]
- Swedish Research Council
- Swedish Cancer Society
- Wallenberg Academy Fellow program
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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.
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.
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