Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

BACKGROUND: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the target gene expression at post-transcriptional level. They are widely involved in biological processes, such as embryonic development, cell division, differentiation, and apoptosis. Evidence suggests that miRNAs can constrain the variation of their target to buffer the fluctuation of expression. However, whether this effect can act on the genome-wide expression remains controversial. RESULTS: In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations. CONCLUSIONS: Our study confirmed that the genetic buffering roles of miRNAs can act on genome expression fluctuation and provides insights into how miRNAs and transcription factors coordinate to cope with external perturbation.