Designing small multiple-target artificial RNAs.
Designing small multiple-target artificial RNAs.
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DOI：
10.1093/nar/gkq354
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发表时间：
2010-07
影响因子：
14.9
通讯作者：
Ferbeyre G
中科院分区：
文献类型：
--
作者：
De Guire V;Caron M;Scott N;Ménard C;Gaumont-Leclerc MF;Chartrand P;Major F;Ferbeyre G
MicroRNAs （miRNAs）是一种自然产生的小rna，可以调节几种基因的表达。mirna的靶向规则基于其成熟产物与靶基因mrna之间的序列互补。基于我们目前对这些规则的理解，我们开发了一种算法来设计人工mirna，同时靶向一组预定的基因。为了在计算机上验证我们的算法，我们测试了已知由单个miRNA靶向的不同组基因。该算法在溶液中找到相应的miRNA种子，其中还包括可能靶向这些基因的新的人工miRNA序列种子。我们还验证了一些同时靶向E2F家族成员的人工mirna的功能。这些人工mirna在正常人类成纤维细胞和前列腺癌细胞中复制了E2Fs抑制的效果，它们抑制细胞增殖并诱导细胞衰老。我们得出结论，目前基于种子序列的miRNA靶向规则可以设计多靶点的人工miRNA。这种方法可能在研究和治疗中都有应用。
MicroRNAs (miRNAs) are naturally occurring small RNAs that regulate the expression of several genes. MiRNAs’ targeting rules are based on sequence complementarity between their mature products and targeted genes’ mRNAs. Based on our present understanding of those rules, we developed an algorithm to design artificial miRNAs to target simultaneously a set of predetermined genes. To validate in silico our algorithm, we tested different sets of genes known to be targeted by a single miRNA. The algorithm finds the seed of the corresponding miRNA among the solutions, which also include the seeds of new artificial miRNA sequences potentially capable of targeting these genes as well. We also validated the functionality of some artificial miRNAs designed to target simultaneously members of the E2F family. These artificial miRNAs reproduced the effects of E2Fs inhibition in both normal human fibroblasts and prostate cancer cells where they inhibited cell proliferation and induced cellular senescence. We conclude that the current miRNA targeting rules based on the seed sequence work to design multiple-target artificial miRNAs. This approach may find applications in both research and therapeutics.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
DOI：
10.1083/jcb.200603039
发表时间：
2006-10-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rosenberg MI;Georges SA;Asawachaicharn A;Analau E;Tapscott SJ
通讯作者：
Tapscott SJ
影响因子：
5.3
作者：
Hossain, Anwar;Kuo, Macus T.;Saunders, Grady F.
通讯作者：
Saunders, Grady F.
MicroRNA-21下调人胶质母细胞瘤细胞T98G中肿瘤抑制因子PDCD4的表达
影响因子：
9.7
作者：
Chen, Yang;Liu, Wei;Peng, Xiaozhong
通讯作者：
Peng, Xiaozhong