Making sense of antisense microRNAs

Three independent papers in the January 1st issue of G&D report on the discovery of a bidirectionally transcribed microRNA (miRNA) locus in Drosophila. The studies from Drs. Alexander Stark and Manolis Kellis (MIT) and colleagues, and from Dr. Eric Lai (MSKCC) and colleagues, both reveal that antisense transcription of the Hox miRNA locus, miR-iab-4, generates the novel miRNA precursor mir-iab-8, which is processed into active regulatory RNAs. When ectopically expressed, mir-iab-8 generates homeotic phenotypes via direct repression of Hox gene targets. The paper from Dr. Welcome Bender (Harvard Medical School) demonstrates that knock out of miR-iab-4 reveals the existence of a miRNA transcribed from the opposite strand. Furthermore, the loss of the antisense miRNA causes subtle derepression of a hox gene and results in sterility of the mutant flies. The identification of additional antisense miRNAs in Drosophila and mammals suggests this as a mechanism that may contribute to the diversification of miRNA function.