Abstract:
:RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and their genome-wide effects on miRNA processing have not been determined. We solved the crystal structure of the human Dicer-TRBP interface, revealing the structural basis of the interaction. Interface residues conserved between TRBP and PACT show that the proteins bind to Dicer in a similar manner and by mutual exclusion. Based on the structure, a catalytically active Dicer that cannot bind TRBP or PACT was designed and introduced into Dicer-deficient mammalian cells, revealing selective defects in guide strand selection. These results demonstrate the role of Dicer-associated RNA binding proteins in maintenance of gene silencing fidelity.
journal_name
Mol Celljournal_title
Molecular cellauthors
Wilson RC,Tambe A,Kidwell MA,Noland CL,Schneider CP,Doudna JAdoi
10.1016/j.molcel.2014.11.030subject
Has Abstractpub_date
2015-02-05 00:00:00pages
397-407issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00951-4journal_volume
57pub_type
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