The ribonuclease Dis3 is an essential regulator of the developmental transcriptome.
The ribonuclease Dis3 is an essential regulator of the developmental transcriptome.
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DOI：
10.1186/1471-2164-13-359
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发表时间：
2012-08-01
期刊：
影响因子：
4.4
通讯作者：
Andrulis ED
中科院分区：
文献类型：
--
作者：
Hou D;Ruiz M;Andrulis ED
Dis 3是核糖核酸酶，直接作用于大量不同RNA种类的加工、周转和监视。从真细菌到真核生物进化保守，并且是RNA加工外泌体的关键组分，Dis 3已被证明在酵母和苍蝇S2细胞中是必需的。然而，目前尚不清楚Dis 3是否在后生动物中具有重要功能。本研究探讨了Dis 3是否是果蝇发育和生存所必需的，以及Dis 3如何调节发育中果蝇的转录组。使用转基因苍蝇，我们表明，Dis 3敲低（Dis 3 KD）延缓生长，诱导黑色素瘤的形成，并最终导致2龄幼虫致死。为了确定Dis 3 KD果蝇表型是否是破坏发育调节的RNA周转的结果，我们对从发育阶段动物分离的总RNA进行了RNA深度测序分析。来自Dis 3 KD果蝇的转录本的生物信息学分析揭示了大量的转录组学变化，最显著的是早期表达的RNA的下调。最后，基因本体分析的早期阶段表明，Dis 3调节转录相关的细胞外结构和重塑，神经发生和核苷酸代谢。我们的结论是，Dis 3是必不可少的早期果蝇的发展，并具有特定的和重要的阶段特定的作用，在调节RNA代谢。在显示的第一次，Dis 3是需要一个多细胞生物体的发展，我们的工作提供了机制的洞察如何Dis 3-无论是独立的或与RNA加工外泌体参与细胞类型特异性RNA周转后生动物的发展。
Dis3 is ribonuclease that acts directly in the processing, turnover, and surveillance of a large number of distinct RNA species. Evolutionarily conserved from eubacteria to eukaryotes and a crucial component of the RNA processing exosome, Dis3 has been shown to be essential in yeast and fly S2 cells. However, it is not known whether Dis3 has essential functions in a metazoan. This study inquires whether Dis3 is required for Drosophila development and viability and how Dis3 regulates the transcriptome in the developing fly. Using transgenic flies, we show that Dis3 knock down (Dis3KD) retards growth, induces melanotic tumor formation, and ultimately results in 2nd instar larval lethality. In order to determine whether Dis3KD fly phenotypes were a consequence of disrupting developmentally regulated RNA turnover, we performed RNA deep sequencing analysis on total RNA isolated from developmentally staged animals. Bioinformatic analysis of transcripts from Dis3KD flies reveals substantial transcriptomic changes, most notably down-regulation in early expressed RNAs. Finally, gene ontology analysis of this early stage shows that Dis3 regulates transcripts related to extracellular structure and remodelling, neurogenesis, and nucleotide metabolism. We conclude that Dis3 is essential for early Drosophila melanogaster development and has specific and important stage-specific roles in regulating RNA metabolism. In showing for the first time that Dis3 is required for the development of a multicellular organism, our work provides mechanistic insight into how Dis3—either independent of or associated with the RNA processing exosome—participates in cell type-specific RNA turnover in metazoan development.
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