Proteins are the end products of genes made from mRNA templates, and mRNA is a molecule that acts as a copy of the blueprint for making proteins. There is a difference between the amount of mRNAs and the amount of proteins in a single cell. However, it was not well understood in what kind of cells those quantitative differences are large, and whether genes with quantitative differences have important functions for the cell.

In this study, the amounts of mRNAs and proteins were comprehensively analyzed using pluripotent stem cells such as human iPS cells and ES cells, and skin cells (human dermal fibroblasts: HDFs) from which iPS cells are derived. As a result, the researchers identified 228 genes whose mRNA levels in the cells did not change but only protein levels varied. These genes were found to be particularly variable in pluripotent stem cells.

Examining the importance of these genes, they found that 84 genes were important regardless of cell type, but 20 genes were specifically essential for the survival of pluripotent stem cells.

Furthermore, the research group investigated how the amounts of proteins in the three cell types are regulated. The researchers found that there are three gene groups whose protein degradation is enhanced in HDFs and that the subcellular localization of mRNAs varied in most of the 20 genes. These results suggest that protein levels may be regulated by mRNA localization.

This research is one step toward elucidating the regulatory mechanisms of protein amounts.

The results of this research were published in iScience on April 25, 2022.

• doi: 10.1016/j.isci.2022.104289