miRNA processing turned upside down.

MicroRNAs are 19-22 nt-long RNAs that regulate eukaryotic gene expression. They are processed from stem-loop containing precursor transcripts by RNAse III enzymes of the Dicer family. In this issue of the EMBO Journal, a study by Bologna and colleagues investigates the processing of two plant MIRNA families with unusually long precursors. Their findings suggest a non-canonical mode of biogenesis in which DCL1, the plant miRNA-producing enzyme, initiates sequential cuts close to the loop at the tip of the stem rather than at its base. It therefore requires the integrity of the upper stem in the precursor, although the structural and/or sequence features that guide DCL1 to its initial binding platform are yet to be identified. Owing to the loop-to-base processing and the unusual length of the stem, several additional small RNA species are produced before the cognate miRNA is excised, a phenomenon that might shed light on the origin of MIRNA genes.