MicroRNAs - From Mechanism to Organism

Hand-drawn ink & watercolor illustrations for a Review I wrote together with Luisa Cochella on miRNA Biology in animals – Check out the paper for details

FIGURE 1 | The evolutionary origins of miRNAs in eukaryotes. Two key players in small RNA-mediated silencing, Argonaute proteins and RNase III like enzymes, originated in prokaryotes. The miRNA pathway in animals emerged with the birth of the Microprocessor, composed of Drosha and Pasha, in unicellular holozoans. Diverse lineages that branched from the last eukaryotic common ancestor (LECA) also evolved miRNA-like pathways. However, it is still under debate whether these evolved independently in four additional clades: Slime molds, Green algae, Brown Algae, and Land plants or if the pathway was already present in the last common ancestor.

FIGURE 2 | Schematic of the miRNA biogenesis pathway. The different steps leading to production of a mature miRNA are shown. Kinetic studies in Drosophila revealed that biogenesis is fast for most miRNAs but loading into Argonaute represents the rate-limiting step (based on Reichholf et al., 2019).

FIGURE 3 | Canonical miRNA-silencing mechanism in animals. miRNAs elicit repression of target genes usually through a combination of translational repression and promotion of mRNA decay. Argonaute is guided by a miRNA to a cognate target mRNA and tethers GW182, forming the core of the most common animal miRISC.

FIGURE 4 | Alternative outcomes of miRNA-mediated targeting. In addition to the common miRISC effects on translation and stability of target mRNAs, other functional outcomes of miRISC binding to an mRNA are possible. 

FIGURE 5 | Diversification of the metazoan miRNA repertoire. Shown are numbers of individual miRNAs/miRNA-families (in bold) annotated with high confidence for various clades. Number of miRNA families present in the last common ancestors of branching clades are noted above the split. Exemplary organisms depicted are Amphimedon queenslandica, Nematostella vectensis, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, and Homo sapiens.