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腾讯登录Nature：DDRNA在DNA损伤应答中的作用
| 导读 | 随着人们对生物领域研究的深入，非编码RNA(non-coding RNAs, ncRNAs)在一系列生物学事件中的作用被越来越多的发现和认识。比如，一些ncRNA可以在DICER和DROSHA的作用下切割成短的双链小RNA，这些小RNA靶向沉默细胞内的mRNA，这也就是我们常说的RNA干扰。
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随着人们对生物领域研究的深入，非编码RNA(non-coding RNAs, ncRNAs)在一系列生物学事件中的作用被越来越多的发现和认识。比如，一些ncRNA可以在DICER和DROSHA的作用下切割成短的双链小RNA，这些小RNA靶向沉默细胞内的mRNA，这也就是我们常说的RNA干扰。
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DNA损伤应答（DNA-damage response，DDR）是指有机体DNA受到损伤时细胞增殖停滞的一种反应，在DNA损伤发生后，DDR通过募集大量蛋白形成蛋白簇集点，来感应和传导损伤信号。迄今为止，还没有研究把DICER和DROSHA的加工产物与细胞的DDR途径联系起来。
本文中，研究者发现在人类、小鼠和斑马鱼中，DICER和DROSHA是激活DDR途径所必须的，而RNAi途径的下游分子对DDR的激活没有影响。通过对DDR蛋白簇集点和对细胞周期检验点的分析，研究人员指出DDR蛋白簇集点对RNA酶A敏感，而DICER和DROSHA的加工产物在修复RNA酶A处理过的细胞DDR蛋白簇集点中是必须的。通过对RNA深度测序和对双链DNA断裂的细胞中DDR活性的检测，研究人员证明了，DDR蛋白簇集点的形成需要一类小RNA的参与，这类名为DDRNA的小RNA正是DICER与DROSHA的加工产物。该研究揭示了非编码RNA一项意想不到的新功能，同时使我们对DDR途径有了新的认识。
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<a title="" href="http://dx.doi.org/10.1038/nature11061" target="_blank">doi:10.1038/nature11061</a>
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<br/><strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response</strong><br/>
Sofia Francia, Flavia Michelini, Alka Saxena, Dave Tang, Michiel de Hoon, Viviana Anelli, Marina Mione, Piero Carninci & Fabrizio d’Adda di Fagagna
Non-coding RNAs (ncRNAs) are involved in an increasingly recognized number of cellular events1. Some ncRNAs are processed by DICER and DROSHA RNases to give rise to small double-stranded RNAs involved in RNA interference (RNAi)2. The DNA-damage response (DDR) is a signalling pathway that originates from a DNA lesion and arrests cell proliferation3. So far, DICER and DROSHA RNA products have not been reported to control DDR activation. Here we show, in human, mouse and zebrafish, that DICER and DROSHA, but not downstream elements of the RNAi pathway, are necessary to activate the DDR upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. DDR foci are sensitive to RNase A treatment, and DICER- and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, we demonstrate that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11–RAD50–NBS1-complex-dependent manner (MRE11 also known as MRE11A; NBS1 also known as NBN). DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. Our results describe an unanticipated direct role of a novel class of ncRNAs in the control of DDR activation at sites of DNA damage.
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<br/>来源：生物谷
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DNA损伤应答（DNA-damage response，DDR）是指有机体DNA受到损伤时细胞增殖停滞的一种反应，在DNA损伤发生后，DDR通过募集大量蛋白形成蛋白簇集点，来感应和传导损伤信号。迄今为止，还没有研究把DICER和DROSHA的加工产物与细胞的DDR途径联系起来。
本文中，研究者发现在人类、小鼠和斑马鱼中，DICER和DROSHA是激活DDR途径所必须的，而RNAi途径的下游分子对DDR的激活没有影响。通过对DDR蛋白簇集点和对细胞周期检验点的分析，研究人员指出DDR蛋白簇集点对RNA酶A敏感，而DICER和DROSHA的加工产物在修复RNA酶A处理过的细胞DDR蛋白簇集点中是必须的。通过对RNA深度测序和对双链DNA断裂的细胞中DDR活性的检测，研究人员证明了，DDR蛋白簇集点的形成需要一类小RNA的参与，这类名为DDRNA的小RNA正是DICER与DROSHA的加工产物。该研究揭示了非编码RNA一项意想不到的新功能，同时使我们对DDR途径有了新的认识。
<div id="ztload">
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201205/20120524201903969.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1038/nature11061" target="_blank">doi:10.1038/nature11061</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response</strong><br/>
Sofia Francia, Flavia Michelini, Alka Saxena, Dave Tang, Michiel de Hoon, Viviana Anelli, Marina Mione, Piero Carninci & Fabrizio d’Adda di Fagagna
Non-coding RNAs (ncRNAs) are involved in an increasingly recognized number of cellular events1. Some ncRNAs are processed by DICER and DROSHA RNases to give rise to small double-stranded RNAs involved in RNA interference (RNAi)2. The DNA-damage response (DDR) is a signalling pathway that originates from a DNA lesion and arrests cell proliferation3. So far, DICER and DROSHA RNA products have not been reported to control DDR activation. Here we show, in human, mouse and zebrafish, that DICER and DROSHA, but not downstream elements of the RNAi pathway, are necessary to activate the DDR upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. DDR foci are sensitive to RNase A treatment, and DICER- and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, we demonstrate that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11–RAD50–NBS1-complex-dependent manner (MRE11 also known as MRE11A; NBS1 also known as NBN). DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. Our results describe an unanticipated direct role of a novel class of ncRNAs in the control of DDR activation at sites of DNA damage.
</div>
</div>
</div>
<br/>来源：生物谷
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