title: Roles of mRNA fate modulators Dhh1 and Pat1 in TNRC6-dependent gene silencing recapitulated in yeast.
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 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 probably 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 microRNA-induced silencing complex to the decapping machinery as well as the translation apparatus.
authors: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Shiho
authors: S
authors: Makino
authors: the Institute of Molecular and Cellular Biosciences and the Department of Medical Genome Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan, and mishima@iam.u-tokyo.ac.jp.
authors: Yuichiro
authors: Y
authors: Mishima
authors: the Graduate School of Science, Kobe University, Kobe 657-8501, Japan.
authors: Kunio
authors: K
authors: Inoue
authors: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan, tinada@m.tohoku.ac.jp.
authors: Toshifumi
authors: T
authors: Inada
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D026723:Polyadenylation; D014176:Protein Biosynthesis; D034622:RNA Interference; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D012260:Ribonucleases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D001324:Autoantigens; C079592:CDC39 protein, S cerevisiae; D018797:Cell Cycle Proteins; C103266:PAT1 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C570983:TNRC6A protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases
keywords: Gene Silencing; Translation Regulation; Yeast; Zebrafish; mRNA Decay; miRNA Mechanism
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