Shimoni Yishai, Friedlander Gilgi, Hetzroni Guy, Niv Gali, Altuvia Shoshy, Biham Ofer, Margalit Hanah
Racah Institute of Physics, The Hebrew University, Jerusalem, Israel.
Mol Syst Biol. 2007;3:138. doi: 10.1038/msb4100181. Epub 2007 Sep 25.
The importance of post-transcriptional regulation by small non-coding RNAs has recently been recognized in both pro- and eukaryotes. Small RNAs (sRNAs) regulate gene expression post-transcriptionally by base pairing with the mRNA. Here we use dynamical simulations to characterize this regulation mode in comparison to transcriptional regulation mediated by protein-DNA interaction and to post-translational regulation achieved by protein-protein interaction. We show quantitatively that regulation by sRNA is advantageous when fast responses to external signals are needed, consistent with experimental data about its involvement in stress responses. Our analysis indicates that the half-life of the sRNA-mRNA complex and the ratio of their production rates determine the steady-state level of the target protein, suggesting that regulation by sRNA may provide fine-tuning of gene expression. We also describe the network of regulation by sRNA in Escherichia coli, and integrate it with the transcription regulation network, uncovering mixed regulatory circuits, such as mixed feed-forward loops. The integration of sRNAs in feed-forward loops provides tight repression, guaranteed by the combination of transcriptional and post-transcriptional regulations.
小非编码RNA的转录后调控在原核生物和真核生物中均已得到广泛认可。小RNA（sRNA）通过与mRNA碱基互补配对在转录后水平调控基因表达。在此，我们通过动力学模拟对这种调控模式进行表征，并与蛋白质-DNA相互作用介导的转录调控以及蛋白质-蛋白质相互作用实现的翻译后调控进行比较。我们定量研究表明，当需要对外界信号快速做出反应时，sRNA介导的调控具有优势，这与有关其参与应激反应的实验数据一致。我们的分析表明，sRNA-mRNA复合物的半衰期及其生成速率之比决定了靶蛋白的稳态水平，这表明sRNA介导的调控可能对基因表达起到微调作用。我们还描述了大肠杆菌中sRNA介导的调控网络，并将其与转录调控网络整合，从而揭示了诸如混合前馈环等混合调控回路。前馈环中sRNA的整合提供了严格的抑制作用，这由转录调控和转录后调控共同作用来保证。
