Combination of RNA interference and U1 inhibition leads to increased inhibition of gene expression.
Combination of RNA interference and U1 inhibition leads to increased inhibition of gene expression.
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DOI：
10.1093/nar/gkq299
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发表时间：
2010-07
影响因子：
14.9
通讯作者：
Fortes P
中科院分区：
文献类型：
--
作者：
Abad X;Razquin N;Abad A;Fortes P
RNA干扰(RNAi)对基因表达的特异性抑制具有革命性意义。然而，许多siRNAs会引起剂量依赖的不良继发效应，这一事实阻碍了RNAi的应用。因此，需要新的方法来增加低剂量抑制剂对基因表达的抑制。我们测试了RNAi和U1i(U1小核RNA-SnRNA-干扰)的结合。U1i是基于U1抑制物(U1in)，U1SnRNA分子被修饰以靶向Pre-mRNA，并通过阻断核多聚腺苷来抑制其基因表达。RNAi和U1i的结合导致了对报告基因或内源基因的更强的抑制，而不是单独使用这两种技术。观察到的增加的抑制作用随着时间的推移是稳定的，即使在减少抑制剂剂量的情况下，也允许比单独使用任何一种抑制剂获得的最佳抑制作用更高。我们认为，当需要更高的抑制作用或没有有效的抑制剂时，RNAi和U1i的组合将是有意义的。此外，这些技术的结合将允许在减少抑制剂剂量的情况下进行功能抑制，避免因剂量依赖的有害影响而产生的毒性。
RNA interference (RNAi) has been revolutionary for the specific inhibition of gene expression. However, the application of RNAi has been hampered by the fact that many siRNAs induce dose-dependent unwanted secondary effects. Therefore, new methods to increase inhibition of gene expression with low doses of inhibitors are required. We have tested the combination of RNAi and U1i (U1 small nuclear RNA—snRNA—interference). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to target a pre-mRNA and inhibit its gene expression by blocking nuclear polyadenylation. The combination of RNAi and U1i resulted in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. The increased inhibition observed is stable over time and allows higher inhibition than the best obtained with either of the inhibitors alone even with decreased doses of the inhibitors. We believe that the combination of RNAi and U1i will be of interest when higher inhibition is required or when potent inhibitors are not available. Also, the combination of these techniques would allow functional inhibition with a decreased dose of inhibitors, avoiding toxicity due to dose-dependent unwanted effects.
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