Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response.
Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response.
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果蝇 tsRNA 通过反义配对优先抑制一般翻译机制并参与细胞饥饿反应。
DOI：
10.1093/nar/gky189
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发表时间：
2018-06-01
影响因子：
14.9
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Luo S;He F;Luo J;Dou S;Wang Y;Guo A;Lu J
转移RNA衍生的小RNA（transferRNA-derivedsmallRNAs，tsRNAs）是一类新兴的小RNA，但其调控作用尚不清楚。在这里，我们研究了果蝇中tsRNA介导的调节的分子机制和后果。通过分析495个公开的小RNA文库，我们证明大多数tsRNA在果蝇中是保守的，普遍的和丰富的。通过对转染单链tsRNA模拟物和模拟物的S2细胞进行mRNA测序和核糖体分析，我们表明，tsRNA通过保守的互补序列匹配识别靶mRNA，并通过翻译抑制抑制靶基因。靶点预测表明，tsRNA优先抑制一般翻译机制的关键组分的翻译，这解释了tsRNA如何抑制全局mRNA翻译。血清饥饿实验证实，tsRNA通过优先靶向核糖体蛋白和翻译起始或延伸因子参与细胞饥饿反应。在正常和饥饿条件下S2细胞中AGO 2的敲低揭示了对AGO 2的tsRNA介导的调节的依赖性。我们还用荧光素酶报告基因测定验证了代表性的tsRNA对细胞全局翻译和特异性靶点的抑制作用。我们的研究表明，tsRNA介导的调节可能是至关重要的能量稳态和代谢适应的细胞系统。
Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition. The target prediction suggests that tsRNAs preferentially suppress translation of the key components of the general translation machinery, which explains how tsRNAs inhibit the global mRNA translation. Serum starvation experiments confirm tsRNAs participate in cellular starvation responses by preferential targeting the ribosomal proteins and translational initiation or elongation factors. Knock-down of AGO2 in S2 cells under normal and starved conditions reveals a dependence of the tsRNA-mediated regulation on AGO2. We also validated the repressive effects of representative tsRNAs on cellular global translation and specific targets with luciferase reporter assays. Our study suggests the tsRNA-mediated regulation might be crucial for the energy homeostasis and the metabolic adaptation in the cellular systems.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
核糖体分析揭示了果蝇果蝇中普遍存在的终止密码子读取。
影响因子：
7.7
作者：
Dunn JG;Foo CK;Belletier NG;Gavis ER;Weissman JS
通讯作者：
Weissman JS
影响因子：
64.5
作者：
Demetriades C;Doumpas N;Teleman AA
通讯作者：
Teleman AA
影响因子：
64.5
作者：
Foerstemann, Klaus;Horwich, Michael D.;Zamore, Phillip D.
通讯作者：
Zamore, Phillip D.
影响因子：
7
作者：
Artieri CG;Fraser HB
通讯作者：
Fraser HB