Complexity of murine cardiomyocyte miRNA biogenesis, sequence variant expression and function.

microRNAs (miRNAs) are critical to heart development and disease. Emerging research indicates that regulated precursor processing can give rise to an unexpected diversity of miRNA variants. We subjected small RNA from murine HL-1 cardiomyocyte cells to next generation sequencing to investigate the relevance of such diversity to cardiac biology.

mRNA isoform diversity can obscure detection of miRNA-mediated control of translation.

Reporter-based studies support inhibition of translation at the level of initiation as a substantial component of the miRNA mechanism, yet recent global analyses have suggested that they predominantly act through decreasing target mRNA stability. Cells commonly coexpress several processing isoforms of an mRNA, which may also differ in their regulatory untranslated regions (UTR). In particular, cancer cells are known to express high levels of short 3' UTR isoforms that evade miRNA-mediated regulation, whereas longer 3' UTRs predominate in nontransformed cells.