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Published Online July 12, 2001
Science DOI: 10.1126/science.1062961

Research Articles

Submitted on May 30, 2001
Accepted on July 3, 2001

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

György Hutvágner 1, Juanita McLachlan 1, 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.

* To whom correspondence should be addressed. E-mail: phillip.zamore{at}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.


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