Positive correlation between ADAR expression and its targets suggests a complex regulation mediated by RNA editing in the human brain

Figures & data

Table 1. Number of target genes and background genes used in the analyses.

	ABA-2013	Kang-2011
All targets	7,864	6,834
Intronic Alus	7,494	6,525
3’UTR Alus	1,024	878
5’UTR Alus	92	55
CDS Alus	38	37
Background genes	12,909	10,731

Figure 1. ADAR and ADARB1 expression in the human brain based on the ABA-2013 data set. Heat map of normalized mRNA expression in 3 coronal slices of a human brain. Expression levels were calculated here by first summing expression over smaller regions, and then dividing by the maximum expression over regions, and averaged over 6 adult brains. This was done to allow easier visualization of the expression levels in the different brain regions. (A) ADAR expression is enriched in the cingulate gyrus - CG, the pons - P, the claustrum - C and the medulla oblongata - MO. (B) ADARB1 expression is enriched in the thalamus - TH), the pons - P and the cerebellar cortex - CBC. Figures were created using the brain-expression-visualizer tool available from www.chechiklab.biu.ac.il.

Figure 2. The distribution of spatial correlation values between ADAR and targets (orange) and between ADAR and a background set (light blue). The results are shown for (A) ABA-2013 dataset (B) Kang-2011 data set. The two distributions differ due to 2 groups of genes: a larger number of target genes have positive correlations with ADAR, and there also exist a group of genes that do not contain Alus, thus are not targeted by ADAR, but are strongly negatively correlated with ADAR. (C) Boxplot of the log-transformed p-values of a one-sided Wilcoxon test between ADAR correlations with targets vs. a background set of genes is plotted against the location of the Alu repeat pairs in the gene (note that Alu in the CDS or 5’ UTR is rare). P-values for the 2 datasets are pooled and shown together. Error bars encompass data within 1.5 times the inter-quartile range, and the boxes show the lower and upper quartiles together with the median. Outliers are represented as circles. Lack of differences in correlation between editing at the 3’ UTR and introns argues against global gene regulation by editing at the 3’ UTR. (D,E) 2D histograms of the correlation of genes with ADAR vs. the number of Alu repeats the genes contain. Positive correlation with ADAR increases with number of Alus. Points with more than 50 Alu repeats were ignored for easier visualization. The results are shown for (D) ABA-2013 data set (E) Kang-2011 dataset.

Figure 3. ADAR-target correlations over development. The distribution of spatial correlation values between ADAR and targets with intronic Alus (orange) and between ADAR and a background set (blue), at 2 developmental time points: (A) 10-13 PCW and (B) 6-12 months. (C) Differential co-expression of ADAR and targets. Heatmap of Spearman correlation rho values showing the temporal cross-correlation between target gene lists ranked by their correlation with ADAR.