PUBLICATION
Roles of mRNA-fate modulators Dhh1 and Pat1 in TNRC6-dependent gene silencing recapitulated in yeast
- Authors
- Makino, S., Mishima, Y., Inoue, K., Inada, T.
- ID
- ZDB-PUB-150207-1
- Date
- 2015
- Source
- The Journal of biological chemistry 290(13): 8331-47 (Journal)
- Registered Authors
- Inoue, Kunio, Mishima, Yuichiro
- Keywords
- gene silencing, mRNA decay, miRNA mechanism, translation regulation, yeast, zebrafish
- MeSH Terms
-
- Animals
- Autoantigens/physiology*
- Cell Cycle Proteins/metabolism
- DEAD-box RNA Helicases/physiology*
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Fungal
- Polyadenylation
- Protein Biosynthesis
- RNA Interference
- RNA Stability
- RNA, Fungal/genetics
- RNA, Fungal/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- RNA-Binding Proteins/physiology*
- Ribonucleases/metabolism
- Saccharomyces cerevisiae/genetics*
- Saccharomyces cerevisiae/metabolism
- Saccharomyces cerevisiae Proteins/metabolism
- Saccharomyces cerevisiae Proteins/physiology*
- Transcription Factors/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/physiology*
- PubMed
- 25657010 Full text @ J. Biol. Chem.
Citation
Makino, S., Mishima, Y., Inoue, K., Inada, T. (2015) Roles of mRNA-fate modulators Dhh1 and Pat1 in TNRC6-dependent gene silencing recapitulated in yeast. The Journal of biological chemistry. 290(13):8331-47.
Abstract
The CCR4-NOT complex, the major deadenylase in eukaryotes, plays crucial roles in gene expression at the levels of transcription, mRNA decay, and protein degradation. GW182/TNRC6 proteins, which are core components of the microRNA-induced silencing complex (miRISC) in animals, stimulate deadenylation and repress translation via recruitment of the CCR4-NOT complex. Here we report a heterologous experimental system that recapitulates the recruitment of CCR4-NOT complex by TNRC6 in S. cerevisiae. Using this system, we characterize conserved functions of the CCR4-NOT complex. The complex stimulates degradation of mRNA from the 5' end by Xrn1, in a manner independent of both translation and deadenylation. This degradation pathway is likely conserved in miRNA-mediated gene silencing in zebrafish. Furthermore, the mRNA-fate modulators Dhh1 and Pat1 redundantly stimulate mRNA decay, but both factors are required for poly(A) tail-independent translation repression by tethered TNRC6A. Our tethering-based reconstitution system reveals that the conserved architecture of Not1/CNOT1 provides a binding surface for TNRC6, thereby connecting miRISC to the decapping machinery as well as the translation apparatus.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping