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The Mechanism of RNase III Action: How Dicer Dices

  • Chapter
Book cover RNA Interference

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 320))

Abstract

Members of the Ribonuclease III (RNase III) family are double-stranded (ds) RNA-specific endoribonucleases, characterized by a signature motif in their active centers and a 2-nucleotide (nt) 3′ overhang in their products. Dicer functions as a dsRNA-processing enzyme, producing small interfering RNA (siRNA) of approx. 24 nt in length (approx. 20-basepair RNA duplex with a 2-nt 3′ overhang on each end). Bacterial RNase III functions not only as a processing enzyme, but also as a binding protein that binds dsRNA without cleaving it. As a processing enzyme it produces siRNA-like RNA of approx. 13 nt in length (approx. 9-basepair duplex with a 2-nt 3′ overhang on each end) as well as various types of mature RNA. Dicer is structurally most complicated member of the family; bacterial RNase III is comparatively much simpler. One structure is known for Dicer in its RNA-free form (MacRae, Zhou, Li, Repic, Brooks, Cande, Adams, and Doudna, Science 311:195–198); many structures are available for bacterial RNase III, including the first catalytic complex of the entire family (Gan, Tropea, Austin, Court, Waugh, and Ji, Cell 124:355–366). In light of the structural and biochemical information on the RNase III proteins and the structure of a non-Dicer PAZ (Piwi Argonaute Zwille) domain in complex with a 7-basepair RNA duplex with a 2-nt 3′ overhang on each end (Ma, Ye, and Patel, Nature 429:318–322), the structure and function of Dicer is being elucidated.

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Abbreviations

Aa-RNase III:

Aquifex aeolicus RNase III

Ago:

Argonaute

ds:

Double-stranded

dsRBD:

dsRNA-binding domain

endoND:

Endonuclease domain

Ec-RNase III:

Escherichia coli RNase III

Gi-Dicer:

Giardia intestinalis Dicer

Hs-Agol:

Homo sapiens Agol

Hs-Dicer:

Homo sapiens Dicer

nt:

Nucleotide

PAZ:

Piwi Argonaute Zwille

PDB:

Protein Data Bank

siRNA:

Small interfering RNA

ss:

Single-stranded

RISC:

RNA-induced silencing complex

RMSD:

Root-mean-square deviation

RNAi:

RNA interference

RNase III:

Ribonuclease III

Sp-Dicer:

Schizosaccharomyces pombe Dicer

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Authors and Affiliations

  1. Macromolecular Crystallography laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702-1201, USA

    Xinhua Ji

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  1. Xinhua Ji
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Editors and Affiliations

  1. Cold Spring Harbor Laboratory, Cold Spring Harbor Fellows Program, Cold Spring Harbor, NY, 11771

    Patrick J. Paddison

  2. Department of Molecular & Experimental Medicine Division of Oncovirology, The Scripps Research Institute, 10550 N. Torrey Pines Road, BCC-239, La Jolla, CA, 92037, USA

    Peter K. Vogt

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Ji, X. (2008). The Mechanism of RNase III Action: How Dicer Dices. In: Paddison, P.J., Vogt, P.K. (eds) RNA Interference. Current Topics in Microbiology and Immunology, vol 320. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75157-1_5

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