title: miRISC recruits decapping factors to miRNA targets to enhance their degradation.
abstract: 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.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nishihara
authors.forename: Latifa
authors.initials: L
authors.lastname: Zekri
authors.forename: Joerg E
authors.initials: JE
authors.lastname: Braun
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D020169:Caspases; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*
chemical_list: C489654:AGO1 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C513405:Gw protein, Drosophila; D035683:MicroRNAs; C549399:Patr-1 protein, Drosophila; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C532748:Me31B protein, Drosophila; D020169:Caspases; C103568:Dcp-1 protein, Drosophila; D053487:DEAD-box RNA Helicases