Target Dependent Coordinated Biogenesis Ensures Cascaded Expression of miRNAs in Activated Murine Macrophage

Abstract

AbstractMicroRNAs (miRNAs) repress protein expression by binding to the 3’ UTR of the target mRNAs. By exploring the effect of target mRNA on biogenesis of cognate miRNAs, we have noted miRNA with higher number of binding sites (primary miRNA) coordinates the biogenesis and activity of another miRNA (secondary miRNA) having binding sites on the 3’ UTR of a common target mRNA. From the quantitative data obtained from macrophage cells, we detected miR-146a-5p as a “primary” miRNA that coordinates biogenesis of “secondary” miR-125b, miR-21 or miR-142-3p to target new sets of mRNAs to balance the immune response in activated macrophage cells. Interestingly, target dependent coordinated biogenesis of miRNAs, happening on the rough endoplasmic reticulum attached membrane, ensures a cumulative mode of action of primary and secondary miRNAs on the secondary target mRNAs where a cascaded effect of primary miRNA on its secondary targets has been detected. Extensive computational analysis for the presence of coordinated biogenesis pairs of miRNAs in mammalian cells has also allowed us to construct a coordinate biogenesis repository to determine context specific coordinated biogenesis relationships exists for specific pairs of miRNAs in mammalian cells.Graphical AbstractmiRNA with higher number of binding sites (primary miRNA) can coordinates the biogenesis and activity of another miRNA (secondary miRNA)Target dependent coordinated biogenesis of miRNAs ensures a cumulative mode of action of primary and secondary miRNAs on the secondary target mRNAs on rER attached polysomesmiR-146a-5p acts as a “primary” miRNA to coordinate biogenesis of “secondary” miR-125b, miR-21 or miR-142-3p in activated macrophage cellsCoordinate biogenesis balance the immune response in activated macrophage cells by ensuring propagation of primary miRNAs effect to diverse target mRNAs through secondary miRNAs.