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

机译:优先调节人类基因组中稳定表达的基因表明microRNA具有广泛的表达缓冲作用

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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.
机译:背景MicroRNA(miRNA)是一类小的非编码RNA,它们在转录后水平上调控靶基因的表达。它们广泛参与生物学过程,例如胚胎发育,细胞分裂,分化和凋亡。有证据表明,miRNA可以限制其靶标的变异,以缓冲表达的波动。但是,这种作用是否可以作用于全基因组表达仍存在争议。结果在本研究中,我们通过大规模微阵列数据的荟萃分析,全面探讨了人类基因组中稳定表达的基因(SE基因)和波动基因(FL基因)。我们发现这些基因具有不同的功能分布。通过使用miRNA调控的倾向性分析显示,miRNA靶标显着丰富了SE基因,支持了miRNA可以缓冲整个基因组表达波动的假说。 miRNA的表达缓冲作用与3'非翻译区内的靶位点数目无关。此外,我们发现基因表达波动与启动子区域中转录因子结合位点的数量呈正相关,这表明转录因子与miRNA之间的协调导致对外部干扰的平衡反应。结论我们的研究证实了miRNA的遗传缓冲作用可以作用于基因组表达波动,并为miRNA和转录因子如何协调以应对外部干扰提供了见识。

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