Figure 2.

Modes of microRNA emergence in plants and animals. (a) Left: intragenomic duplications of protein-coding genes (or non-coding regions) can generate long foldbacks, which can be diced into small RNAs capable of targeting the progenitor transcript. This phenomenon seems common in plants, where extensive target complementarity is the rule, and ancestral relationships between microRNAs (miRNAs) and their targets can sometimes be detected; Drosophila hairpin RNA (hpRNA) may emerge similarly. MITE, miniature inverted-repeat transposable element. Right: inverted repeats might also emerge from initially unstructured sequences. This appears to be the dominant mode of miRNA emergence in animals. It also occurs in plants, but only rarely do such miRNAs appear to acquire functional targets. (b) Inferred model for plant miRNA emergence from long foldbacks; arrows indicate evolutionary relationships, arrowheads indicate small RNAs produced from a given hairpin. Long hairpins are processed haphazardly, often by different Dicers, to generate heterogeneous small interfering RNAs (siRNAs). As regulatory relationships are refined, the precision and phasing of hairpin processing may increase. Shortening of the hairpin to produce a single defined duplex may represent a mature state of plant miRNA evolution. (c) Expansion of miRNA clusters. In both plants and animals, local duplication may increase the dosage of a given miRNA. In animals, there may be an advantage for Drosha cleavage of hairpins emerging near extant miRNAs, leading to operons of unrelated miRNAs. (d) Different biogenesis mechanisms impose distinct demands on gene birth. Mirtrons need only evolve the capacity for one RNase III cleavage by Dicer, whereas canonical miRNAs need to gain the ability to be cleaved consecutively by Drosha and Dicer.