Abstract
Extensive research has established how miRNAs regulate target mRNAs by translation repression and/or endonucleolytic degradation in metazoans. However, information related to the effect of target mRNA on biogenesis and stability of corresponding miRNAs in animals is limited. Here we report regulated biogenesis of cognate miRNAs by their target mRNAs. Enhanced pre-miRNA processing by AGO-associated DICER1 contributes to this increased miRNP formation. The processed miRNAs are loaded onto AGO2 to form functionally competent miRISCs both in vivo and also in a cell-free in vitro system. Thus, we identify an additional layer of posttranscriptional regulation that helps the cell to maintain requisite levels of mature forms of respective miRNAs by modulating their processing in a target-dependent manner, a process happening for miR-122 during stress reversal in human hepatic cells.
Highlights
Extensive research has established how miRNAs regulate target mRNAs by translation repression and/or endonucleolytic degradation in metazoans
It has been shown that once the AGO2 is loaded with the miRNA, the miRNA Induced Silencing Complex (miRISC) dissociates from the miRNA loading complex (miRLC) and the loaded miRISC can catalyse multiple rounds of repression and target RNA cleavage[16]
Using in vitro RISC-loading assay systems, we identify that increased processivity of AGO2-associated DICER1 in the presence of target mRNA contributes to higher biogenesis of mature miRNA from the pre-miRNA
Summary
Extensive research has established how miRNAs regulate target mRNAs by translation repression and/or endonucleolytic degradation in metazoans. We report regulated biogenesis of cognate miRNAs by their target mRNAs. Enhanced pre-miRNA processing by AGO-associated DICER1 contributes to this increased miRNP formation. We observe target mRNA-dependent biogenesis of mature miR-122 from pre-miR-122 in human hepatoma cells during recovery from amino acids starvation-related stress This eventually leads to the finding that the presence of abundant amounts of mRNA bearing target sites for a particular miRNA induces increased biogenesis of the mature miRNA from the precursor. Using in vitro RISC-loading assay systems, we identify that increased processivity of AGO2-associated DICER1 in the presence of target mRNA contributes to higher biogenesis of mature miRNA from the pre-miRNA
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