Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation.
Data(s) |
24/09/2009
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Resumo |
MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3'UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation. |
Identificador |
http://digitalcommons.library.tmc.edu/uthmed_docs/132 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803087/?tool=pmcentrez |
Publicador |
DigitalCommons@The Texas Medical Center |
Fonte |
UT Medical School Journal Articles |
Palavras-Chave | #Animals #Ascites #Autoantigens #Binding Sites #Carcinoma #Krebs 2 #Cell-Free System #Eukaryotic Initiation Factor-2 #Eukaryotic Initiation Factor-4G #Gene Silencing #Hela Cells #Humans #Kinetics #Mice #MicroRNAs #Poly(A)-Binding Proteins #Protein Biosynthesis #Protein Structure #Tertiary #Proteins #RNA Processing #Post-Transcriptional #RNA Stability #RNA #Messenger #RNA-Induced Silencing Complex #Receptors #CCR4 #Transfection #Carcinoma, Krebs 2 #Protein Structure, Tertiary #RNA Processing, Post-Transcriptional #RNA, Messenger #Receptors, CCR4 #Medicine and Health Sciences |
Tipo |
text |