Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense Mediated mRNA Decay.
Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense Mediated mRNA Decay.
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DOI：
10.1371/journal.pgen.1005857
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发表时间：
2016-05
期刊：
影响因子：
4.5
通讯作者：
Jessberger R
中科院分区：
文献类型：
--
作者：
Fanourgakis G;Lesche M;Akpinar M;Dahl A;Jessberger R
类染色体（CB）是精子发生特异性的细胞器，其功能尚不清楚。CB含有各种RNA种类、RNA相关蛋白和tudor结构域家族的蛋白质，如TDRD 6，其是适当CB结构所需的。纯化CB的蛋白质组分析揭示了无义介导的mRNA衰变（NMD）机制，包括UPF1的组件。TDRD6对于UPF1定位于CB、UPF1-UPF2和UPF1-MVH相互作用是必需的。在去除TDRD 6后，几种mRNA与UPF 1和UPF 2的结合被扰乱，并且长3 'UTR刺激的但不是下游外显子-外显子连接触发的NMD途径受损。长3'UTR mRNA与UPF1和UPF2的缔合减少与稳定性增加和翻译活性增强相关。因此，我们鉴定CB内的TDRD6为mRNA降解所需，特别是延长的3'UTR触发的NMD途径，并为精子发生中需要NMD提供证据。这种功能依赖于TDRD6促进的CB中mRNA和衰变酶的组装。含Tudor结构域蛋白6（TDRD 6）是雄性生殖细胞中类染色体体（CB）的核心成分。存在于精子细胞中的类染色体含有RNA和蛋白质，不被膜包围，通常位于细胞核附近。在没有TDRD 6的情况下，观察到了一个非常扭曲的CB结构，这项工作要求TDRD 6对精子细胞的功能贡献。我们发现，TDRD6是需要本地化的RNA降解机制的CB。这种所谓的无义介导的衰变（NMD）机制，从体细胞中已知，破坏具有过早终止密码子的mRNA。TDRD6的缺失显著削弱了NMD的一种特定机制，该机制依赖于转录物的长3 '非翻译区。因此，CB部件TDRD 6在CB中的国家导弹防御系统机构的装配中起作用。
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. Tudor-domain containing protein 6 (TDRD6) is a central component of the chromatoid body (CB) in male germ cells. Chromatoid bodies, which are present in spermatids, contain RNA and protein, are not enclosed by membranes, and typically reside close to the nucleus. Without TDRD6, a much distorted CB structure is observed, and this work asked for the functional contribution of TDRD6 to spermatids. We found that TDRD6 is required for localization of an RNA degradation machinery to the CB. This so-called nonsense mediated decay (NMD) machinery, known from somatic cells, destroys mRNAs that feature premature stop codons. Absence of TDRD6 significantly impairs one specific mechanism of NMD, which depends on long 3’ untranslated regions of the transcripts. Thus, the CB component TDRD6 acts in the assembly of the NMD machinery in the CB.