State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
Commun Biol. 2024 Nov 4;7(1):1431. doi: 10.1038/s42003-024-07162-w.
MicroRNAs (miRNAs) are post-transcriptional, non-coding regulatory RNAs that function coordinately with transcription factors (TFs) in gene regulatory networks. TFs and their targets are often co-regulated by miRNAs, forming composite feedforward circuits (cFFCs) with varying degrees of redundancy, primarily mediated by miRNAs. However, the maintenance of miRNA-mediated regulatory redundancy and its impact on gene expression evolution remain elusive. By integrating ChIP-seq data from ENCODE and miRNA targeting from TargetScanFly, we quantified miRNA-mediated cFFC redundancy in Drosophila melanogaster embryos and larvae, revealing more than three quarters of miRNA targets are involved in redundant cFFCs. Higher cFFC redundancy, where more miRNAs target the same gene within a cFFC, is correlated with stronger purifying selection, reduced expression divergence between species, and increased expression stability under heat shock stress. Redundant cFFCs primarily regulate older or broadly expressed young genes. These findings highlight the role of miRNA-mediated cFFC redundancy in enhancing gene expression robustness through natural selection.
微小 RNA（miRNAs）是转录后、非编码的调控 RNA，它们与基因调控网络中的转录因子（TFs）协同作用。TFs 和它们的靶标通常被 miRNAs 共同调控，形成具有不同程度冗余的复合前馈电路（cFFCs），主要由 miRNAs 介导。然而，miRNA 介导的调节冗余的维持及其对基因表达进化的影响仍然难以捉摸。通过整合 ENCODE 的 ChIP-seq 数据和 TargetScanFly 的 miRNA 靶向，我们量化了果蝇胚胎和幼虫中 miRNA 介导的 cFFC 冗余，发现超过四分之三的 miRNA 靶标参与冗余的 cFFC。更高的 cFFC 冗余，即同一个 cFFC 中有更多的 miRNAs 靶向同一个基因，与更强的纯化选择、物种间表达差异减少以及热休克应激下表达稳定性增加相关。冗余的 cFFC 主要调控较老或广泛表达的年轻基因。这些发现强调了 miRNA 介导的 cFFC 冗余通过自然选择增强基因表达稳健性的作用。
