Global signatures of protein and mRNA expression levels

Abstract

Cellular states are determined by differential expression of the cell's proteins. The relationship between protein and mRNA expression levels informs about the combined outcomes of translation and protein degradation which are, in addition to transcription and mRNA stability, essential contributors to gene expression regulation. This review summarizes the state of knowledge about large-scale measurements of absolute protein and mRNA expression levels, and the degree of correlation between the two parameters. We summarize the information that can be derived from comparison of protein and mRNA expression levels and discuss how corresponding sequence characteristics suggest modes of regulation.

Fig. 1

Essential steps in gene expression. Genes are expressed by production of mRNAs from DNA, and protein from mRNAs. Much interest has been paid to the ‘first half’ of these processes, e.g. transcription regulation. This review focuses on the ‘second half’ of these processes, in particular translation and protein degradation and how these influence the number of protein molecules observed per mRNA.

Fig. 2

Elements of eukaryotic translation and protein degradation regulation. The number of protein molecules present per mRNA is influenced both by translation and protein degradation. Both rates are regulated by several processes whose signals are encoded in the mRNA and protein sequences. Transcription and mRNA degradation (stability) affect the steady-state concentrations of mRNAs, but not (formally) the protein-per-mRNA ratio—the latter of which is the focus of this review. Some processes, e.g. binding of miRNAs or RNA-binding proteins, affect both translation and mRNA stability.

Fig. 3

Protein versus mRNA concentrations across organisms. (A, B and C). Protein and mRNA concentrations correlate to a large extent across bacteria, yeast and human. Data for E. coli were taken from ref. ; the yeast proteomics data were averaged from concentrations reported in ref. – and , as well as RNA concentrations from ref. , and . The human data are from ref. : Daoy medulloblastoma cellular lysate was analyzed via LC-MS/MS on an LTQ-Orbitrap and protein concentrations for 1025 proteins were estimated using APEX. mRNA concentrations were estimated using Nimblegen arrays, (D) across years. The graph shows the correlations for three different groups of organisms (bacteria, uni- and multi-cellular eukaryotes), with data points colored according to significance of the correlation. White data points are non-significant correlation coefficients.