<figcaption> Credit: © 2004 NATURE PUBLISHING GROUP</figcaption>

With all the hubbub surrounding microRNAs in plants and invertebrates after their discovery, it was only a matter of time before a functional role was found in mammals. In 2004, graduate student Soraya Yekta, and Whitehead Institute for Biomedical Research member David Bartel found a role for microRNA miR-196 in HOXB8 regulation in mice.1 Naturally, it was assumed such a mechanism would exist in mammals. But, says Victor Ambros, microRNA pioneer at Dartmouth Medical School, "Nothing about microRNAs is particularly expected, so it really is important to actually find these situations."

Yekta and colleagues demonstrated that in 15-to-17-day old mouse embryos HOXB8 mRNA is cleaved precisely 10 nucleotides from the 5' end of the miR-196 complementarity sequence. Recently Bartel, with Cliff Tabin of Harvard Medical School, showed that miR-196 expression, limited to the hindlimb, blocks induction of HOXB8 by retinoic acid.2 But...

Bartel's lab has shown that more than one-third of human genes are under selective pressure to maintain miRNA complementarity, while thousands of others are under pressure to avoid it. Bartel predicts, "When considering also the potential for non-conserved targeting, the vast majority of mammalian genes are either regulated by miRNAs or they are avoiding miRNAs." We'll see how this assumption plays out.


1. S. Yekta et al., "MicroRNA-directed cleavage of HOXB8 mRNA," Science, 304:594-6, 2004. (Cited 129 times) 2. E. Hornstein et al., "The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development," Nature, 438:671-4, Dec. 1, 2005.

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