EMD-5603
Substrate-specific structural rearrangements of human Dicer
EMD-5603
Single-particle31.0 Å
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Map released: 01/05/2013
Last modified: 19/06/2013
Sample Organism:
Homo sapiens
Sample: Human Dicer in complex with pre-let7
Deposition Authors: Taylor DW
,
Ma E,
Shigematsu H
,
Cianfrocco MA
,
Noland CL,
Nagayama K,
Nogales E,
Doudna JA,
Wang HW
Sample: Human Dicer in complex with pre-let7
Deposition Authors: Taylor DW
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Substrate-specific structural rearrangements of human Dicer.
Taylor DW
,
Ma E,
Shigematsu H
,
Cianfrocco MA
,
Noland CL,
Nagayama K,
Nogales E,
Doudna JA,
Wang HW
(2013) Nat. Struct. Mol. Biol. , 20 , 662 - 670
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(2013) Nat. Struct. Mol. Biol. , 20 , 662 - 670
Abstract:
Dicer has a central role in RNA-interference pathways by cleaving double-stranded RNAs (dsRNAs) to produce small regulatory RNAs. Human Dicer can process long double-stranded and hairpin precursor RNAs to yield short interfering RNAs (siRNAs) and microRNAs (miRNAs), respectively. Previous studies have shown that pre-miRNAs are cleaved more rapidly than pre-siRNAs in vitro and are the predominant natural Dicer substrates. We have used EM and single-particle analysis of Dicer-RNA complexes to gain insight into the structural basis for human Dicer's substrate preference. Our studies show that Dicer traps pre-siRNAs in a nonproductive conformation, whereas interactions of Dicer with pre-miRNAs and dsRNA-binding proteins induce structural changes in the enzyme that enable productive substrate recognition in the central catalytic channel. These findings implicate RNA structure and cofactors in determining substrate recognition and processing efficiency by human Dicer.
Dicer has a central role in RNA-interference pathways by cleaving double-stranded RNAs (dsRNAs) to produce small regulatory RNAs. Human Dicer can process long double-stranded and hairpin precursor RNAs to yield short interfering RNAs (siRNAs) and microRNAs (miRNAs), respectively. Previous studies have shown that pre-miRNAs are cleaved more rapidly than pre-siRNAs in vitro and are the predominant natural Dicer substrates. We have used EM and single-particle analysis of Dicer-RNA complexes to gain insight into the structural basis for human Dicer's substrate preference. Our studies show that Dicer traps pre-siRNAs in a nonproductive conformation, whereas interactions of Dicer with pre-miRNAs and dsRNA-binding proteins induce structural changes in the enzyme that enable productive substrate recognition in the central catalytic channel. These findings implicate RNA structure and cofactors in determining substrate recognition and processing efficiency by human Dicer.