Abstract
MicroRNAs are short non-coding RNAs that are evolutionarily conserved and are pivotal post-transcriptional mediators of gene regulation. Together with transcription factors and epigenetic regulators, they form a highly interconnected network whose building blocks can be classified depending on the number of molecular species involved and the type of interactions amongst them. Depending on their topology, these molecular circuits may carry out specific functions that years of studies have related to the processing of gene expression noise. In this review, we first present the different over-represented network motifs involving microRNAs and their specific role in implementing relevant biological functions, reviewing both theoretical and experimental studies. We then illustrate the recent advances in synthetic biology, such as the construction of artificially synthesised circuits, which provide a controlled tool to test experimentally the possible microRNA regulatory tasks and constitute a starting point for clinical applications.
Highlights
Life as we see it is the result of the complex regulation of organisms’ gene expression, required to fulfil vital biological tasks
Tsang and colleagues [6] developed a computational method for analysing gene expression data, and the results indicated that two classes of circuits are enriched in the human genome, namely miRNA mediated feedback and feedforward loops (FFLs)
The results showed that miR-1199-5p acts in a double negative feedback loop (DNFL) with the previously mentioned transcription factors (TFs) ZEB1, and the behaviour of the circuit seems similar to that of the miR-200 family [99]
Summary
Life as we see it is the result of the complex regulation of organisms’ gene expression, required to fulfil vital biological tasks This complexity is well reflected by the intricate network of interactions between the thousands of genes constituting genomes. Even though the single miRNA–target interaction seldom displays phenotypic outcomes, a number of works suggest that single miRNAs or families involved in a broader interactome, where their alteration might give rise to cascade-like consequences, can concretely affect cell state and function. A number of studies have addressed the relationship between miRNA and noise, and the results suggested that miRNAs could provide precision to protein expression by buffering noise when needed [37,43] or either exploit stochasticity in biological contexts that take advantage of gene expression variability, such as differentiation processes [44,45].
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