The Inside-Out Mechanism of Dicers from Budding Yeasts
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Bartel_The inside-out.pdf
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Author(s)
Weinberg, David E.
Nakanishi, Kotaro
Patel, Dinshaw J.
Bartel, David
Weinberg, David E.
Date Issued
July 2011
Journal
Cell
Publisher
Elsevier B.V.
Citation
Weinberg, David E., Kotaro Nakanishi, Dinshaw J. Patel, and David P. Bartel. “The Inside-Out Mechanism of Dicers from Budding Yeasts.” Cell 146, no. 2 (July 2011): 262-276. © 2011 Elsevier Inc.
Version
Final published version
Abstract
The Dicer ribonuclease III (RNase III) enzymes process long double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that direct RNA interference. Here, we describe the structure and activity of a catalytically active fragment of Kluyveromyces polysporus Dcr1, which represents the noncanonical Dicers found in budding yeasts. The crystal structure revealed a homodimer resembling that of bacterial RNase III but extended by a unique N-terminal domain, and it identified additional catalytic residues conserved throughout eukaryotic RNase III enzymes. Biochemical analyses showed that Dcr1 dimers bind cooperatively along the dsRNA substrate such that the distance between consecutive active sites determines the length of the siRNA products. Thus, unlike canonical Dicers, which successively remove siRNA duplexes from the dsRNA termini, budding-yeast Dicers initiate processing in the interior and work outward. The distinct mechanism of budding-yeast Dicers establishes a paradigm for natural molecular rulers and imparts substrate preferences with ramifications for biological function.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.06.021
