Normally, the hairpin's curve, called the "loop" is subsequently cut out by another enzyme called Dicer, leaving behind a double-stranded "stem". This is the mature microRNA that gets picked up by Ago2. One strand is eventually discarded; the other Ago2-bound strand is ready to seek out and trigger the destruction of its messenger RNA target.

Hannon's team has found however, that miR-451 maturation proceeds via a different pathway, where the Dicer step is skipped and the immature hairpin is directly loaded into Ago2. "Ago2 then essentially performs its slicing job to complete the maturation of this microRNA," Cheloufi explains. The team attributes the ability to Ago2 to bind to the immature miR-451 hairpin to its unique structure that is also highly conserved in vertebrates.

"The existence of this alternative pathway explains some of the evolutionary pressure to maintain a catalytically active Argonaute protein in animals," says Hannon. His team is now hunting for other RNA molecules that might be similarly generated and that might be critical for normal embryogenesis.

"A dicer-independent miRNA biogenesis pathway that requires Ago catalysis" appears as an advance online publication on April 27th in Nature. The full citation is: Sihem Cheloufi, Camila O. Dos Santos, Mark M. W. Chong & Gregory J. Hannon. The paper is available at nature/nature/journal/vnfv/ncurrent/abs/nature09092.html

Source: Cold Spring Harbor Laboratory