Transcriptome-wide regulation of pre-mRNA splicing and expression by the RNA-binding protein Quaking during monocyte to macrophage differentiation [Microarray]

Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Microarray analysis of gene expression and splicing in THP-1 cells transfected with shRNAs, with or without PMA treatment to induce differentiation. 12 total samples were analyzed: THP-1 monocytic cell line transfected with QKI or control shRNAs; samples taken at day 0 or day 3 of PMA-induced differentiation into macrophages.