التفاصيل البيبلوغرافية
| العنوان: |
Dicer-TRBP Complex Formation Ensures Accurate Mammalian MicroRNA Biogenesis. |
| المؤلفون: |
Wilson, Ross C.1, Tambe, Akshay1, Kidwell, Mary Anne1, Noland, Cameron L.1, Schneider, Catherine P.1, Doudna, Jennifer A.1,2,3,4 doudna@berkeley.edu |
| المصدر: |
Molecular Cell. Feb2015, Vol. 57 Issue 3, p397-407. 11p. |
| مصطلحات موضوعية: |
*GENE silencing, *MICRORNA, *ORIGIN of life, *CARRIER proteins, *CRYSTAL structure |
| مستخلص: |
Summary 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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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