ABSTRACT Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are unique because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this separation is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database MirGeneDB to 45 organisms that represent the full taxonomic breadth of Metazoa. By consistently annotating and naming more than 10,900 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked more than 2,100 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct Metazoan evolution. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs but also biomedical and biomarker research. MirGeneDB is publicly and freely available at http://mirgenedb.org/ .

MirGeneDB 2.0: The metazoan microRNA complement