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Insights into the regulation of protein abundance from proteomic and transcriptomic analyses

Abstract

Recent advances in next-generation DNA sequencing and proteomics provide an unprecedented ability to survey mRNA and protein abundances. Such proteome-wide surveys are illuminating the extent to which different aspects of gene expression help to regulate cellular protein abundances. Current data demonstrate a substantial role for regulatory processes occurring after mRNA is made — that is, post-transcriptional, translational and protein degradation regulation — in controlling steady-state protein abundances. Intriguing observations are also emerging in relation to cells following perturbation, single-cell studies and the apparent evolutionary conservation of protein and mRNA abundances. Here, we summarize current understanding of the major factors regulating protein expression.

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Figure 1: Modes of translation and protein-degradation regulation.
Figure 2: Relationships between mRNA and protein abundances, as observed in large-scale proteome- and transcriptome-profiling experiments.

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Acknowledgements

The authors acknowledge support from the US National Institutes of Health and the Welch Foundation (F1515, to E.M.M.). We also thank T. Lionnet for helpful discussions.

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Correspondence to Christine Vogel or Edward M. Marcotte.

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Glossary

High-resolution tandem mass spectrometry

The use of two consecutive mass spectrometry steps to measure mass-to-charge ratios for peptides and their fragment ions, respectively. Modern technology enables a mass accuracy of <0.01 Da.

Nanoflow chromatography

In the context of peptides, this method separates a peptide mixture by differences in biophysical properties. It operates at flow rates of nanolitres per minute to increase separation efficiency and decrease sample volumes.

PEST sequences

Protein sequence motif enriched for proline (P), glutamate (E), serine (S) and threonine (T) that serves as a protein degradation signal.

Ribosome footprinting

Identification of ribosomal binding sites on mRNA through ribosome stalling and next-generation sequencing of the bound RNA fragments.

Stable isotopic labelling with amino acids in cell culture

(SILAC). A widely used technique for estimating relative protein concentrations by mass spectrometry.

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Vogel, C., Marcotte, E. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 13, 227–232 (2012). https://doi.org/10.1038/nrg3185

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