MicroRNA-mediated gene regulation and the resilience of multicellular animals

Abstract

MicroRNAs are small RNAs that enable parts of the genome to regulate the other parts of the genome by RNA::RNA complementarity. Genes that encode microRNAs function as trans-acting regulators of hundreds of other genes, primarily by inhibiting the production of protein from mRNAs to which the microRNAs can bind by base pairing. MicroRNAs and their Argonaute partner proteins constitute a regulatory complex (the miRISC) that exhibits astonishing regulatory versatility. microRNAs have been shown to perform diverse roles in genetic regulatory networks (GRNs) – to control developmental switches, to dampen gene expression noise, to coordinate multigene functional modules, and more broadly, to confer robustness and resilience to developmental and homeostatic processes. Genetic analysis reveals that the function of particular microRNAs can be conditional, such that the microRNA is required under particular environmental or physiological conditions, but relatively dispensable under other conditions. The diversity and versatility of microRNA function in animal systems reflects the many ways that miRISC can be regulated by cellular signaling pathways, and the structure-function interplay among microRNA, target, and Argonaute.