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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 2 - Biochemistry (E. Izaurralde)     Display Documents



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ID: 695231.0, MPI für Entwicklungsbiologie / Abteilung 2 - Biochemistry (E. Izaurralde)
miRISC recruits decapping factors to miRNA targets to enhance their degradation
Authors:Nishihara, T.; Zekri, L.; Braun, J. E.; Izaurralde, E.
Language:English
Date of Publication (YYYY-MM-DD):2013-10
Title of Journal:Nucleic Acids Research
Journal Abbrev.:Nucleic Acids Res
Volume:41
Issue / Number:18
Start Page:8692
End Page:8705
Sequence Number of Article:23863838
Review Status:Internal review
Audience:Experts Only
Abstract / Description:MicroRNA (miRNA)-induced silencing complexes (miRISCs) repress translation and promote degradation of miRNA targets. Target degradation occurs through the 5'-to-3' messenger RNA (mRNA) decay pathway, wherein, after shortening of the mRNA poly(A) tail, the removal of the 5' cap structure by decapping triggers irreversible decay of the mRNA body. Here, we demonstrate that miRISC enhances the association of the decapping activators DCP1, Me31B and HPat with deadenylated miRNA targets that accumulate when decapping is blocked. DCP1 and Me31B recruitment by miRISC occurs before the completion of deadenylation. Remarkably, miRISC recruits DCP1, Me31B and HPat to engineered miRNA targets transcribed by RNA polymerase III, which lack a cap structure, a protein-coding region and a poly(A) tail. Furthermore, miRISC can trigger decapping and the subsequent degradation of mRNA targets independently of ongoing deadenylation. Thus, miRISC increases the local concentration of the decapping machinery on miRNA targets to facilitate decapping and irreversibly shut down their translation.
Free Keywords:Animals; Argonaute Proteins/metabolism; DEAD-box RNA Helicases/metabolism; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics/metabolism; Eukaryotic Initiation Factor-4E/metabolism; MicroRNAs/*metabolism; *RNA Stability; RNA, Messenger/chemistry/*metabolism; RNA-Binding Proteins/metabolism; RNA-Induced Silencing Complex/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:root
Affiliations:MPI für Entwicklungsbiologie/Abteilung 2 - Biochemie (Elisa Izaurralde)
Identifiers:ISSN:1362-4962 (Electronic) 0305-1048 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/23863838 [ID No:2]
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