Simultaneous quantification of mRNA and protein in single cells reveals post-transcriptional effects of genetic variation

Abstract

<i>Trans</i>-acting DNA variants may specifically affect mRNA or protein levels of genes located throughout the genome. However, prior work compared <i>trans</i>-acting loci mapped in separate studies, many of which had limited statistical power. Here, we developed a CRISPR-based system for simultaneous quantification of mRNA and protein of a given gene via dual fluorescent reporters in single, live cells of the yeast <i>Saccharomyces cerevisiae</i>. In large populations of recombinant cells from a cross between two genetically divergent strains, we mapped 86 <i>trans</i>-acting loci affecting the expression of ten genes. Less than 20% of these loci had concordant effects on mRNA and protein of the same gene. Most loci influenced protein but not mRNA of a given gene. One locus harbored a premature stop variant in the <i>YAK1</i> kinase gene that had specific effects on protein or mRNA of dozens of genes. These results demonstrate complex, post-transcriptional genetic effects on gene expression.