2012年5月23日，Nature在線發表了義大利分子腫瘤研究所首席研究員 Fabrizio d'Adda di Fagagna 課題組的一篇題為Site-specific DICER and DROSHA RNA products control the DNA-damage response的科研論文，報導了一種新的非編碼小RNA 用於在DNA損傷部位控制DNA 損傷反應的激活。
DNA損傷反應機制包括細胞的染色體DNA損傷監控和修復機制，是維護基因組穩定性的重要機制之一。DNA損傷反應( DNA damage response ，DDR)系統對腫瘤的發生、發展及治療具有重要的作用。
MicroRNA（miRNA）是近幾年在真核生物中發現的一類具有調控功能的非編碼RNA，它們主要參與基因轉錄後水平的調控。miRNA基因的轉錄初產物 (pri-miRMA)很快被一種核糖核酸酶ⅢDrosha加工成為miRNA前體 (pre—miRNA)，然後由細胞核轉運至細胞質中，經另一種核糖核酸酶ⅢDicer識別剪切為成熟miRNA。至今，關於Dicer和 Drosha 加工而成的非編碼RNA 激活DNA損傷反應，還未見報導。
本研究發現，DDR聚焦點（foci）對核糖核酸酶A的處理非常敏感。在核糖核酸酶A處理的細胞中，需要Dicer和 Drosha依賴的RNA產物修復DDR聚焦點。還發現，Dicer和 Drosha對於激活DNA損傷反應是必須的，而不是RNA幹擾信號通路中的下遊元件。
通過對DNA雙鏈斷鏈切口的RNA深度測序（deep sequencing）和DNA損傷反應激活的研究，證明了DDR聚焦點的形成需要位點專一的依賴Dicer和 Drosha的 小 RNA。此小RNA被稱為DDRNAs。
DDRNAs，無論由化學合成還是由Dicer加工而來，對於修復RNase-A處理的細胞來說，都是足夠的。在不存在其他細胞內RNA時也是如此。
本研究不僅發現了一種新的非編碼RNA，而且拓寬了對非編碼RNA功能的理解和認識。(生物谷Bioon.com）
Site-specific DICER and DROSHA RNA products control the DNA-damage response
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.