Fig. 4
Alternative polyadenylation usage and m6A methylation in the aging brain. a, d Cumulative frequency plot showing the preference for proximal or distal 3′ UTR usage for genes at the 6-week and 52-week developmental stages. At 52 weeks, there is a global decrease in the log2 proximal/distal ratio compared to 6 weeks, indicating that genes prefer distal 3′ UTRs. b Differentially hypermethylated genes at 52 weeks preferentially display a m6A methylation peak in the alternative UTR (aUTR) compared to the canonical UTR (cUTR). IGV screenshot showing differential methylation in the aUTR of Uba3 at 52 weeks and not in 6 weeks. c Bar graph showing a highly significant decrease in the mRNA level of Uba3 at 52 weeks compared to 6 weeks. **p value < 0.01. d Cumulative frequency plot showing the correlation between APA usage and mRNA levels in cUTR differentially methylated genes compared to genes that display differential methylation in the aUTR. Differentially methylated genes with methylation in the aUTR have a larger log2 TPM 6wk/52wk ratio compared to genes that show cUTR differential methylation at 52 weeks. This indicates that aUTR differential methylation correlates with a markedly more significant decrease in mRNA levels compared to genes that are differentially methylated in the cUTR at 52 weeks. e Gene ontology analysis of enriched reactome pathways of genes that show aUTR differential methylation at 52 weeks. These pathways would be affected in the aging process