Several previous reports have concluded that RNA levels cannot be used to predict protein levels. However, in a new study from KTH Royal Institute of Technology, published in the journal Molecular Systems Biology scientists from the Human Protein Atlas show that protein levels can be predicted from RNA levels if a gene-specific RNA-to-protein factor is used.

The human genome consists of DNA, a molecule that contains the instructions needed to build and maintain cells. For the instructions to be carried out, DNA must be read and transcribed into RNA transcripts that can be used to produce protein. The transcriptome is a collection of all the transcripts present in a cell. An important issue for molecular biology is to establish if transcript levels of a given gene can be used as proxies for the corresponding protein levels.

In the present study, the researchers have developed a mass spectrometry-based method that is sensitive and reproducible in order 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.

Fredrik Edfors is the first author of the study.

– We show that the transcript and protein levels do not correlate well unless a gene- specific RNA-to-protein (RTP) conversion factor independent of the cell or tissue-type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels, he says.

– The RTP-ratio varies several orders of magnitude between different genes, from a few hundred to several hundred thousands and is seemingly conserved across different cell types and tissues.

These new data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell.

– There are many efforts around the world to systematically determine the transcript levels in cells, tissues and organs, involving new technologies such as single cell genomics and spatial transcriptomics, Mathias Uhlen, the study leader and professor at KTH, says.

– Our data suggest that the knowledge-based transcriptomics resources created as part of these efforts will be valuable also for protein studies, thus forming an attractive link between the field of genomics and proteomics.

Read the whole paper Gene-specific correlation of RNA and protein levels in human cells and tissues

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