György Hutvágner 1, a, Juanita McLachlan 1, a, Amy E. Pasquinelli 2, Éva Bálint 3, Thomas Tuschl 4, Phillip D. Zamore 1*
1 Department of Biochemistry and Molecular Pharmacology,
University of Massachusetts Medical School, Worcester, MA 01655, USA.
2 Department of Molecular Biology, Massachusetts General
Hospital and Department of Genetics, Harvard Medical School, Boston, MA
02114, USA.
3 Department of Cell Biology, University of Massachusetts
Medical School, Worcester, MA 01655, USA.
4 Department of Cellular Biochemistry, Max-Planck-Institute
for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
a These authors contributed equally to this work.
* To whom correspondence should be addressed. E-mail: phillip.zamore@umassmed.edu
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.
1. "Conservation of the Sequence and Temporal Expression of let-7 Heterochronic Regulatory RNA".
2. "Activation of DNA Transcription within Repressed Chromatin by Nuclear RNA Species".
3. "Perspective: Dicing Up RNAs".