Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene Expression Dynamics

Lack of prominent developmental defects arising from loss of many individual miRNAs is consistent with the observations of collaborative networks between miRNAs and roles for miRNAs in regulating stress responses. However, these characteristics may only partially explain the seemingly nonessential nature of many miRNAs. Non-miRNA gene expression regulatory mechanisms also collaborate with miRNA-induced silencing complex (miRISC) to support robust gene expression dynamics. Genetic enhancer screens have revealed roles of miRNAs and other gene repressive mechanisms in development or other cellular processes that were masked by genetic redundancy. Besides discussing the breadth of the non-miRNA genes, we use LIN-28 as an example to illustrate how distinct regulatory systems, including miRNAs and multiple protein stability mechanisms, work at different levels to target expression of a given gene and provide tissue-specific and stage-specific regulation of gene expression. miRNA pathways converge with diverse non-miRNA regulatory mechanisms to regulate common targets. Convergent regulation at different levels of gene expression imparts tissue-specific functions, synergy, and precise temporal gene regulation. Proteolytic pathways provide a strong commitment in gene regulation since proteolysis is irreversible without new protein synthesis. Genetic redundancy remains a critical barrier in understanding genomic architecture and regulatory networks. Genes with known functions may have additional important non-canonical functions.