| First Author | Wilson RC | Year | 2015 |
| Journal | Mol Cell | Volume | 57 |
| Issue | 3 | Pages | 397-407 |
| PubMed ID | 25557550 | Mgi Jnum | J:219753 |
| Mgi Id | MGI:5629650 | Doi | 10.1016/j.molcel.2014.11.030 |
| Citation | Wilson RC, et al. (2015) Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Mol Cell 57(3):397-407 |
| abstractText | RNA-mediated gene silencing in human cells requires the accurate generation of approximately 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. |
