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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Taylor DW,Ma E,Shigematsu H,Cianfrocco MA,Noland CL,Nagayama K,Nogales E,Doudna JA,Wang HWdoi
10.1038/nsmb.2564subject
Has Abstractpub_date
2013-06-01 00:00:00pages
662-70issue
6eissn
1545-9993issn
1545-9985pii
nsmb.2564journal_volume
20pub_type
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