title: Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense Mediated mRNA Decay.
abstract: Chromatoid bodies (CBs) are spermiogenesis-specific organelles of largely unknown function. CBs harbor various RNA species, RNA-associated proteins and proteins of the tudor domain family like TDRD6, which is required for a proper CB architecture. Proteome analysis of purified CBs revealed components of the nonsense-mediated mRNA decay (NMD) machinery including UPF1. TDRD6 is essential for UPF1 localization to CBs, for UPF1-UPF2 and UPF1-MVH interactions. Upon removal of TDRD6, the association of several mRNAs with UPF1 and UPF2 is disturbed, and the long 3' UTR-stimulated but not the downstream exon-exon junction triggered pathway of NMD is impaired. Reduced association of the long 3' UTR mRNAs with UPF1 and UPF2 correlates with increased stability and enhanced translational activity. Thus, we identified TDRD6 within CBs as required for mRNA degradation, specifically the extended 3' UTR-triggered NMD pathway, and provide evidence for the requirement of NMD in spermiogenesis. This function depends on TDRD6-promoted assembly of mRNA and decay enzymes in CBs.
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Fanourgakis
authors.affiliation: Deep Sequencing Group SFB 655, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Mathias
authors.identifier: 0000-0002-3274-7163
authors.initials: M
authors.lastname: Lesche
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Müge
authors.initials: M
authors.lastname: Akpinar
authors.affiliation: Deep Sequencing Group SFB 655, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dahl
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072417:Protein Domains / Q000235:genetics; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D013087:Spermatids / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C529051:4-methoxy-1-tyrosyl-gamma-glutamyl-cysteinyl-glycine; D002352:Carrier Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C517521:TDRD6 protein, mouse; C529977:Upf2 protein, mouse; D005978:Glutathione