First published online November 21, 2008
Development 135, 2401e (2008)
© The Company of Biologists Limited
MicroRNAs: they're a knock-out
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.

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Related articles in Development:
- Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126
- Frank Kuhnert, Michael R. Mancuso, Jessica Hampton, Kryn Stankunas, Tomoichiro Asano, Chang-Zheng Chen, and Calvin J. Kuo
Development 2008 135: 3989-3993.
[Abstract]
[Full Text]