Figure 1.
A. Distribution of genome-wide decay profiles across the timecourse experiment (x-axis), where each decay curve shows the decrease in gene expression level (y-axis) relative to the untreated time point. Each line represents the gene-specific median decay profile, while the darkness of the lines indicates the number of genes sharing that decay profile (darker indicates more genes). B. Representative examples of individual-specific decay profiles (dotted lines) for two genes: NFKBIE (in red), which decays faster than average and DCTN2 (in blue), which decays slower than average. Solid lines indicate the gene-specific median decay profile across all 70 individuals.
Figure 2.
Genomic features influencing variation in decay rates across genes.
A. Distributions of gene length (left) and 3′UTR length (right) for genes decaying slower (blue) or faster (red) than average. B. Distributions of the number of miRNA binding sites (normalized by 3′UTR length; y-axis) for genes decaying slower (blue) or faster (red) than average. C. Distributions of AREScores (y-axis) for genes decaying slower (blue) or faster (red) than average. D. Motifs that are significantly over- (yellow) or under-represented (blue) in fast or slow decaying genes. The MI refers to the mutual information score from the FIRE algorithm.
Figure 3.
Relationship between gene expression levels and mRNA decay rates across genes.
A. Genome-wide scatterplot of median decay rates (x-axis) versus median steady-state expression levels (y-axis) for all genes (black dots, where higher densities are in dark colors), slow decaying genes (blue dots), and fast decaying genes (red dots). B. Genes that are within the top 5% (yellow) or top 10% (blue) of both the decay rate and steady-state gene expression. C. Boxplots of the distribution of steady-state expression levels (y-axis) in genes decaying slower (blue) or faster (red) than average.
Table 1.
Genes with discordant decay rates and steady-state gene expression levels.
Figure 4.
Relationship between gene expression levels and mRNA decay rates across individuals.
A. QQ-plot of the t-statistics for association between steady-state expression levels and decay rates across individuals (y-axis) compared to the null distribution of t-statistics assessed by permutations (x-axis). The sign of the t-statistic indicates the direction of correlation. Genes with concordant relationships (orange) have negative t-statistics and genes with discordant relationships (purple) have positive t-statistics. B. Density distributions of the Pearson correlations (x-axis) between mRNA decay rates and PolII reads for genes with either concordant (orange) or discordant (purple) relationships between decay rates and steady-state expression levels across individuals.
Figure 5.
Genome-wide identification of rdQTLs and representative examples.
A. QQ-plot for all tests of association between mRNA decay rates and variants within a cis region of 25 kb around the target gene (y-axis) compared to a null distribution of p-values based on permutations (x-axis). B. QQ-plot for all tests of association between the most significant eQTL SNP for a gene and the mRNA decay rate for the same gene (y-axis) compared to a null distribution of p-values based on permutations (x-axis). C. Example of an rdQTL with concordant eQTL-rdQTL effects (for the gene DDX55). D. Example of an rdQTL with discordant e-QTL-rdQTL effects (for the gene C17orf97).
Figure 6.
miRNA binding sites are enriched with rdQTLs.
The QQ-plots of expected versus observed quantiles of the –log10(p-values) testing the null hypothesis that there is no association between the SNP and RNA decay, for all 3′UTR SNPs (red) and in two known 3′UTR functional annotations – predicted miRNA binding sites (dark blue) and AU-rich element pentamers (light blue).