Importance of translation and nonnucleolytic ago proteins for on-target RNA interference.
Importance of translation and nonnucleolytic ago proteins for on-target RNA interference.
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DOI：
10.1016/j.cub.2008.07.072
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发表时间：
2008-09-09
期刊：
影响因子：
9.2
通讯作者：
Belasco, Joel G.
中科院分区：
文献类型：
--
作者：
Wu, Ligang;Fan, Jihua;Belasco, Joel G.
In animals, both siRNAs and miRNAs are thought to diminish protein synthesis from transcripts that are perfectly complementary by directing endonucleolytic cleavage where they anneal, thereby triggering rapid degradation of the entire message. By contrast, partially complementary messages are downregulated by a combination of translational repression and accelerated decay caused by rapid poly(A) tail removal. Here we present evidence that translational repression can also make a substantial contribution to the downregulation of fully complementary messages by RNA interference. Unlike mRNA destabilization, this inhibitory effect on translation is greater for perfectly complementary elements located in the 3′ untranslated region rather than in the protein-coding region. In addition to known disparities in their endonucleolytic activity, the four Ago proteins with which siRNAs associate in humans differ significantly in their capacity to direct translational repression. As a result, the relative effect of siRNA on targets that are fully versus partially complementary is influenced by the comparative abundance of the three non-nucleolytic Ago proteins, causing this on-target/off-target ratio to vary in a cell-type-dependent manner due to the dissimilar tissue distribution of these proteins. These findings have important implications for the efficacy and specificity of RNA interference.
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影响因子：
46.9
作者：
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通讯作者：
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DOI：
10.1073/pnas.1630797100
发表时间：
2003-08-19
影响因子：
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作者：
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通讯作者：
Zamore, Phillip D.