Bocci Federico, Jolly Mohit Kumar, Levine Herbert, Onuchic José Nelson
Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Department of Chemistry, Rice University, Houston, TX, USA.
Methods Mol Biol. 2019;1912:341-366. doi: 10.1007/978-1-4939-8982-9_14.
RNA is mostly known for its role in protein synthesis, where it encodes information for protein sequence in its messenger RNA (mRNA) form (translation). Yet, RNA molecules regulate several cellular processes other than translation. Here, we present an overview of several mathematical models that help understanding and characterizing the role of noncoding RNA molecules (ncRNAs) in regulating gene expression and protein synthesis. First, we discuss relatively simple models where ncRNAs can modulate protein synthesis via targeting a mRNA. Then, we consider the case of feedback interactions between ncRNAs and their target proteins, and discuss several biological applications where these feedback architectures modulate a cellular phenotype and control the levels of intrinsic and extrinsic noise. Building from these simple circuit motifs, we examine feed-forward circuit motifs involving ncRNAs that generate precise spatial and temporal patterns of protein expression. Further, we investigate the competition between ncRNAs and other endogenous RNA molecules and show that the cross talk between coding and noncoding RNAs can form large genetic circuits that involve up to hundreds of chemical species. Finally, we discuss the role of ncRNAs in modulating cell-cell signaling pathways and therefore the dynamics of spatiotemporal pattern formation in a tissue.
RNA主要因其在蛋白质合成中的作用而为人所知，在蛋白质合成过程中，它以信使RNA（mRNA）的形式编码蛋白质序列的信息（翻译）。然而，RNA分子除了调节翻译外，还调控多种细胞过程。在此，我们概述了几种数学模型，这些模型有助于理解和描述非编码RNA分子（ncRNAs）在调控基因表达和蛋白质合成中的作用。首先，我们讨论相对简单的模型，即ncRNAs可通过靶向mRNA来调节蛋白质合成。然后，我们考虑ncRNAs与其靶蛋白之间的反馈相互作用情况，并讨论这些反馈结构调节细胞表型以及控制内在和外在噪声水平的几种生物学应用。基于这些简单的电路基序，我们研究涉及ncRNAs的前馈电路基序，这些基序可产生精确的蛋白质表达时空模式。此外，我们研究了ncRNAs与其他内源性RNA分子之间的竞争，并表明编码RNA与非编码RNA之间的相互作用可形成涉及多达数百种化学物质的大型遗传电路。最后，我们讨论ncRNAs在调节细胞间信号通路以及组织中时空模式形成动态方面的作用。
