A meta-analysis revealed insights into the sources, conservation and impact of microRNA 5′-isoforms in four model species

MicroRNA (miRNA) 5 0 -isoforms, or 5 0 -isomiRs, are small-RNA species that originate from the same genomic loci as the major miRNAs with their 5 0 ends shifted from the 5 0 ends of the miRNAs by a few nucleotides. Although 5 0 -isomiRs have been reported, their origins, properties and potential functions remain to be examined. We systematically studied 5 0 -isomiRs in human, mouse, fruitfly and worm by analysing a large collection of small non-coding RNA and mRNA profiling data. The results revealed a broad existence of 5 0 -isomiRs in the four species, many of which were conserved and could arise from genomic loci of canonical and non-canonical miRNAs. The well-conserved 5 0 -isomiRs have several features, including a preference of the 3p over the 5p arms of hairpins of conserved mammalian miRNAs, altered 5 0 -isomiRs across species and across tissues, and