A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the <i>let-7</i> Small Temporal RNA

TLDR

The 21‑nt small temporal RNA let‑7 regulates developmental timing in *C. elegans* and likely other bilaterians, and both the let‑7 and RNA‑interference pathways depend on Dicer to generate active small RNAs that repress gene expression. The study aims to show that in *Drosophila melanogaster* a developmentally regulated precursor RNA is cleaved by an RNA‑interference‑like mechanism to produce mature let‑7 stRNA. The authors used in vivo and in vitro experiments to demonstrate that a developmentally regulated precursor RNA is cleaved by an RNA‑interference‑like mechanism to generate mature let‑7 stRNA in *Drosophila melanogaster*.

Abstract

The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals. We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA. Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression.