Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis
Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis
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DOI：
10.1128/jvi.78.23.12868-12876.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Cullen, BR
中科院分区：
文献类型：
--
作者：
Lu, SH;Cullen, BR
虽然植物病毒蛋白抑制RNA干扰(RNAi)已被证明能增强病毒在植物中的复制和致病作用，但到目前为止还没有发现病毒基因产物在脊椎动物细胞中抑制RNAi。在这里，我们提出的证据表明，高度结构类似于160个核苷酸的腺病毒VA1非编码RNA可以在生理水平上抑制RNAi的表达。在腺病毒感染的细胞中高水平表达的VA1能有效地抑制短发夹状RNA(ShRNAs)或人microRNA前体诱导的RNAi，但不影响人工短干扰RNA双链诱导的RNAi。抑制可能是由于抑制了shRNA或前微核糖核酸前体的核输出，竞争Exportin 5核输出因子，以及直接与DICER结合而抑制了DICER功能。综上所述，这些数据争辩说，腺病毒感染可以导致RNAi抑制，并确认VA1 RNA是第一个能够在人类细胞中抑制RNAi的病毒基因产物。
Although inhibition of RNA interference (RNAi) by plant virus proteins has been shown to enhance viral replication and pathogenesis in plants, no viral gene product has as yet been shown to inhibit RNAi in vertebrate cells. Here, we present evidence demonstrating that the highly structured similar to160-nucleotide adenoviral VA1 noncoding RNA can inhibit RNAi at physiological levels of expression. VA1, which is expressed at very high levels in adenovirus-infected cells, potently inhibited RNAi induced by short hairpin RNAs (shRNAs) or human microRNA precursors but did not affect RNAi induced by artificial short interfering RNA duplexes. Inhibition appeared to be due both to inhibition of nuclear export of shRNA or premicro-RNA precursors, competition for the Exportin 5 nuclear export factor, and inhibition of Dicer function by direct binding of Dicer. Together, these data argue that adenovirus infection can result in inhibition of RNAi and identify VA1 RNA as the first viral gene product able to inhibit RNAi in human cells.