Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis.

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 Cell

journal_title

Molecular cell

authors

Wilson RC,Tambe A,Kidwell MA,Noland CL,Schneider CP,Doudna JA

doi

10.1016/j.molcel.2014.11.030

subject

Has Abstract

pub_date

2015-02-05 00:00:00

pages

397-407

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(14)00951-4

journal_volume

57

pub_type

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