Key Roles of MicroRNA-22 Family in Complex Organisms Inferred from its Evolution

Previous studies suggested that microRNAs (miRNAs) participate in almost all cellular processes and the continuous development of miRNA-mediated posttranscriptional regulation might have facilitated the development of complex organisms. Especially, the microRNA-22 (miR-22) family has been recently extensively reported. Here, we accessed the evolution of miR-22 structure, regulation, and targets, and this indicated that miR-22 plays key roles in more complex organisms. We demonstrated that the miR-22 family arose approximate 600 million years ago from the latest common ancestor of bilaterians. Moreover, a survey of genomic contexts and the secondary structure of the miR-22 family revealed that it originated de novo from a relatively conserved intron region, and the mature sequence of the miR-22 family evolved by seed pairing with highly conserved 3' "U" and 5' "G" boundaries. Furthermore, a complete picture of the evolution of the regulatory networks associated with miR-22 was obtained from the analysis of experimentally identified, as well as computationally predicted, functional targets of miR-22.