MicroRNAs (miRNAs), a class of short non-coding RNAs, regulate target messenger RNAs post-transcriptionally by inhibiting their translation or promoting their degradation. The specific roles of miRNAs are only now beginning to be uncovered, but have we inadvertently learned more about their function than we realise? On p. 3989, Calvin Kuo and co-workers report that most of the vascular phenotypes previously attributed to disrupting the mouse gene Egfl7, which encodes an endothelial extracellular matrix molecule, are actually caused by disruption of the endothelial miRNA miR-126, which resides within the seventh intron of Egfl7. miR-126 deletion inhibits VEGF-dependent signalling. Importantly, miR-126 appears to have been unintentionally disrupted in the generation of two knockout mouse models designed to investigate Egfl7 function. As over half of all known miRNAs are embedded in introns of protein-coding genes, and as the mouse genome possibly contains over 1000 miRNAs, this study highlights the importance of considering the potential dysregulation of miRNAs in the design and interpretation of knockout studies.

© 2008.
2008