The
let-7 miRNA (microRNA) is an essential regulator of development from nematode worms to humans. Altered expression of
let-7 results in larval arrest or lethality in Caenorhabditis elegans. Likewise, under- or over-expression of
let-7 in human cells can result in cellular overproliferation or halted cell division respectively. Thus the biogenesis of this critical miRNA is controlled at multiple levels. An unexpected mechanism for regulating the initial processing of
let-7 was recently found to involve the
let-7 miRNA itself. The mature
let-7 miRNA along with its effector protein, Argonaute, were shown to bind to a site in the primary transcripts produced by the
let-7 gene. This interaction enhances processing through a novel auto-regulatory feedback loop. This discovery highlights a new role for the miRNA complex in regulating miRNA biogenesis and enriches the classes of RNAs targeted by Argonaute.