The extent to which RNA stability differs between individuals and its contribution to the interindividual expression variation remain unknown. We conducted a genome-wide analysis of RNA stability in seven human HapMap lymphoblastoid cell lines (LCLs) and analyzed the effect of DNA sequence variation on RNA half-life differences. Twenty-six percent of the expressed genes exhibited RNA half-life differences between LCLs at a false discovery rate (FDR) < 0.05, which accounted for ~ 37% of the gene expression differences between individuals. Nonsense polymorphisms were associated with reduced RNA half-lives. In genes presenting interindividual RNA half-life differences, higher coding GC3 contents (G and C percentages at the third-codon positions) were correlated with increased RNA half-life. Consistently, G and C alleles of single nucleotide polymorphisms (SNPs) in protein coding sequences were associated with enhanced RNA stability. These results suggest widespread interindividual differences in RNA stability related to DNA sequence and composition variation.

Background: Regulation of dopamine D2 receptor (DRD2) is pathophysiologically and pharmacologically important. Results: miR-9 and miR-326 target to the 3Ј-UTR of DRD2, and endogenously inhibit DRD2 expression. A functional single nucleotide polymorphism alters such regulation. Conclusion: DRD2 is post-transcriptionally regulated by miR-326 and miR-9. Significance: The study suggests a pathophysiological and pharmacological role of miR-9 and miR-326 in neuropsychiatric disorders.