Gene-specific Correlation of RNA and Protein Levels in Human Cells and Tissues

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2016 Dec 13

PMID 27951527

Citations 224

Authors

Fredrik Edfors

Frida Danielsson

Bjorn M Hallstrom

Lukas Kall

Emma Lundberg

Fredrik Ponten

Bjorn Forsstrom

Mathias Uhlen

Affiliations

Soon will be listed here.

Abstract

An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.

Citing Articles

High resolution profiling of cell cycle-dependent protein and phosphorylation abundance changes in non-transformed cells.

Rega C, Tsitsa I, Roumeliotis T, Krystkowiak I, Portillo M, Yu L Nat Commun. 2025; 16(1):2579.

PMID: 40089461 DOI: 10.1038/s41467-025-57537-8.

Deciphering motor dysfunction and microglial activation in mThy1--synuclein mice: a comprehensive study of behavioral, gene expression, and methylation changes.

McGregor B, Raihan M, Brishti A, Hur J, Porter J Front Mol Neurosci. 2025; 18:1544971.

PMID: 40018011 PMC: 11865073. DOI: 10.3389/fnmol.2025.1544971.

Human colon stem cells are the principal epithelial responders to bacterial antigens.

de Vries M, de Vries M, Meddens C, Meddens C, Hijma H, Hijma H bioRxiv. 2025; .

PMID: 39975165 PMC: 11839077. DOI: 10.1101/2025.02.07.637053.

The polyphenol metabolite urolithin A suppresses myostatin expression and augments glucose uptake in human skeletal muscle cells.

Wilhelmsen A, Karagounis L, Bennett A, DAmico D, Fouassier A, Jones S Nutr Metab (Lond). 2025; 22(1):12.

PMID: 39962542 PMC: 11834323. DOI: 10.1186/s12986-025-00909-0.

Single-cell transcriptomes reveal cell-type-specific and sample-specific gene function in human cancer.

Yuan H, Liang X, Zhang X, Cao Y Heliyon. 2025; 11(3):e42218.

PMID: 39959484 PMC: 11830296. DOI: 10.1016/j.heliyon.2025.e42218.

References

Forrest A, Kawaji H, Rehli M, Baillie J, de Hoon M, Haberle V . A promoter-level mammalian expression atlas. Nature. 2014; 507(7493):462-70. PMC: 4529748. DOI: 10.1038/nature13182. View

Larsson M, Graslund S, Yuan L, Brundell E, Uhlen M, Hoog C . High-throughput protein expression of cDNA products as a tool in functional genomics. J Biotechnol. 2000; 80(2):143-57. DOI: 10.1016/s0168-1656(00)00258-3. View

Maier T, Schmidt A, Guell M, Kuhner S, Gavin A, Aebersold R . Quantification of mRNA and protein and integration with protein turnover in a bacterium. Mol Syst Biol. 2011; 7:511. PMC: 3159969. DOI: 10.1038/msb.2011.38. View

Lundberg E, Fagerberg L, Klevebring D, Matic I, Geiger T, Cox J . Defining the transcriptome and proteome in three functionally different human cell lines. Mol Syst Biol. 2010; 6:450. PMC: 3018165. DOI: 10.1038/msb.2010.106. View

Payne S . The utility of protein and mRNA correlation. Trends Biochem Sci. 2014; 40(1):1-3. PMC: 4776753. DOI: 10.1016/j.tibs.2014.10.010. View

Cox J, Mann M . MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008; 26(12):1367-72. DOI: 10.1038/nbt.1511. View

Maier T, Guell M, Serrano L . Correlation of mRNA and protein in complex biological samples. FEBS Lett. 2009; 583(24):3966-73. DOI: 10.1016/j.febslet.2009.10.036. View

Gallien S, Duriez E, Crone C, Kellmann M, Moehring T, Domon B . Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol Cell Proteomics. 2012; 11(12):1709-23. PMC: 3518128. DOI: 10.1074/mcp.O112.019802. View

Mortazavi A, Williams B, McCue K, Schaeffer L, Wold B . Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008; 5(7):621-8. DOI: 10.1038/nmeth.1226. View

10.

Mele M, Ferreira P, Reverter F, DeLuca D, Monlong J, Sammeth M . Human genomics. The human transcriptome across tissues and individuals. Science. 2015; 348(6235):660-5. PMC: 4547472. DOI: 10.1126/science.aaa0355. View

11.

Wisniewski J, Zougman A, Nagaraj N, Mann M . Universal sample preparation method for proteome analysis. Nat Methods. 2009; 6(5):359-62. DOI: 10.1038/nmeth.1322. View

12.

Lundberg E, Uhlen M . Creation of an antibody-based subcellular protein atlas. Proteomics. 2010; 10(22):3984-96. DOI: 10.1002/pmic.201000125. View

13.

Studier F . Protein production by auto-induction in high density shaking cultures. Protein Expr Purif. 2005; 41(1):207-34. DOI: 10.1016/j.pep.2005.01.016. View

14.

Anderson L, Seilhamer J . A comparison of selected mRNA and protein abundances in human liver. Electrophoresis. 1997; 18(3-4):533-7. DOI: 10.1002/elps.1150180333. View

15.

Nagaraj N, Wisniewski J, Geiger T, Cox J, Kircher M, Kelso J . Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol. 2011; 7:548. PMC: 3261714. DOI: 10.1038/msb.2011.81. View

16.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

17.

Wilhelm M, Schlegl J, Hahne H, Gholami A, Lieberenz M, Savitski M . Mass-spectrometry-based draft of the human proteome. Nature. 2014; 509(7502):582-7. DOI: 10.1038/nature13319. View

18.

Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J . Corrigendum: Global quantification of mammalian gene expression control. Nature. 2013; 495(7439):126-7. DOI: 10.1038/nature11848. View

19.

Milo R . What is the total number of protein molecules per cell volume? A call to rethink some published values. Bioessays. 2013; 35(12):1050-5. PMC: 3910158. DOI: 10.1002/bies.201300066. View

20.

Bray N, Pimentel H, Melsted P, Pachter L . Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016; 34(5):525-7. DOI: 10.1038/nbt.3519. View