Re-analysis of genome wide data on mammalian microRNA-mediated suppression of gene expression

Abstract

microRNAs are short endogenously expressed RNAs that regulate gene expression post-transcriptionally. Although both mRNA degradation and suppression of mRNA translation can mediate reduced protein levels following microRNA targeting of an mRNA, their relative contributions have remained elusive. A recent genome-wide study in mammals employing RNA-sequencing to measure microRNA effects on mRNA translation and stability concluded that 84?89{%} of microRNA-induced suppression of gene expression is due to degradation of target mRNAs. We re-analyzed this data set and applied a number of analysis modifications which revealed that the contribution of mRNA translation was likely underestimated for some mRNA subsets. Moreover, in contrast to the original analysis, our analysis indicated that suppression of mRNA translation precedes mRNA degradation upon microRNA targeting. Our findings thereby enhance our understanding of microRNA mediated genome wide suppression of gene expression in mammals.