Transcript abundance results from the balance between transcription and mRNA decay, and varies pervasively in humans. We have examined the effect of DNA variation on mRNA half-life differences by conducting a genome-wide survey of mRNA stability in seven human HapMap lymphoblastoid cell lines (LCLs). We determined the mRNA half-life for each gene from the ratio of 4-thio-uridine (4sU)-labeled nascent RNAs to total RNAs. 5,145 (46%) of 11,132 analyzed genes showed inter-individual mRNA half-life differences at a false discovery rate, FDR<0.05. As previously reported, we found transcription to be the main factor influencing transcript abundance. Although mRNA half-life explained only ~6% of transcript abundance on average, it explained ~16% for the subset of genes (~10%) showing inter-individual mRNA half-life differences (P<0.001). We confirmed previously reported correlations of mRNA half-life with transcript length, 3-UTR length, and number of exon-junctions per kb of transcript. The number of miRNA targets in 3-UTRs was negatively correlated with half-life (P=2.210-16), a new observation that is consistent with the role of miRNA in inducing mRNA degradation. Notably, coding GC and GC3 content showed positive correlations with mRNA half-life in genes with inter-individual mRNA half-life differences, implying a role of mRNA stability in shaping synonymous codon usage bias. Consistently, G or C alleles of coding SNPs were found associated with longer mRNA half-life (P=0.021). As expected, we also found that nonsense SNPs were associated with shorter mRNA half-life (P=0.009). Our results strongly suggest that inter-individual mRNA stability differences are widespread and affected by DNA sequence and composition variation.
Genome-wide survey of interindividual differences of RNA stability in human lymphoblastoid cell lines.
Disease, Cell line
View SamplesTumor-infiltrating macrophages, NK cells, CD8+ and CD4+ T cells sorted from clear cell renal cell carcinoma patient specimens. Overall design: 4 macrophage samples (CD45+CD3-CD56-CD14+), 2 CD16+ NK cell samples (CD45+CD3-CD56+CD16+), 5 CD8+ T cell samples (CD45+CD3+CD8+), 3 CD4+ T cell samples (CD45+CD3+CD4+), and one non-immune cell sample (CD45-).
Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures.
Specimen part, Disease, Subject
View Samples