Viral miRNAs
Viral miRNAs
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DOI：
10.1007/978-1-61779-037-9_3
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Renne, Rolf
中科院分区：
文献类型：
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作者：
Plaisance-Bonstaff, Karlie;Renne, Rolf
自2004年以来，在双链DNA病毒（主要是疱疹病毒和多瘤病毒）中发现了200多种microRNAs (miRNAs)（核酸研究，32:D109-D111, 2004）。mirna是一种短的22 +/- 3nt RNA分子，通过结合靶mrna的3'-非翻译区（3' utr）来转录后调节基因表达，从而诱导翻译沉默和/或转录物降解（Nature 431:350- 355,2004; Cell 116:281- 297,2004）。由于miRNA仅需要有限的互补性来结合，因此很难确定miRNA的靶点（Mol Cell 27:91- 105,2007）。迄今为止，仅通过实验验证了相对较少的靶向病毒或宿主细胞基因表达的mirna的靶标：例如，SV40和相关的多瘤病毒编码靶向病毒大T抗原表达的mirna (Nature 435:682-686,2005; J Virol 79:13094-13104, 2005; Virology 383:183-187,2009；α -、β -和γ -疱疹病毒的mirna参与调节从潜伏到裂解基因表达的转变，这是疱疹病毒生命周期的关键步骤。病毒mirna也被证明可以靶向各种宿主细胞基因。尽管这一领域刚刚开始揭示病毒miRNA在生物学和发病机制中的多重作用，但目前的数据强烈表明，病毒编码的miRNA能够调节基本的生物学过程，如免疫识别、促进细胞存活、血管生成、增殖和细胞分化。本章旨在总结我们目前对病毒mirna的了解，它们的靶点和功能，以及它们在病毒生物学、发病机制和γ -疱疹病毒编码的mirna中潜在的肿瘤发生中的作用。
Since 2004, more than 200 microRNAs (miRNAs) have been discovered in double-stranded DNA viruses, mainly herpesviruses and polyomaviruses (Nucleic Acids Res 32:D109-D111, 2004). miRNAs are short 22 +/- 3 nt RNA molecules that posttranscriptionally regulate gene expression by binding to 3'-untranslated regions (3'UTR) of target mRNAs, thereby inducing translational silencing and/or transcript degradation (Nature 431:350-355, 2004; Cell 116:281-297, 2004). Since miRNAs require only limited complementarity for binding, miRNA targets arc difficult to determine (Mol Cell 27:91-105, 2007). To date, targets have only been experimentally verified for relatively few viral miRNAs, which either target viral or host cellular gene expression: For example, SV40 and related polyomaviruses encode miRNAs which target viral large T antigen expression (Nature 435:682-686,2005; J Virol 79:13094-13104, 2005; Virology 383:183-187,2009; J Virol 82:9823-9828,2008) and miRNAs of alpha-, beta-, and gamma-herpesviruses have been implicated in regulating the transition from latent to lytic gene expression, a key step in the herpewirus life cycle. Viral miRNAs have also been shown to target various host cellular genes. Although this field is just beginning to unravel the multiple roles of viral miRNA in biology and pathogenesis, the current: data strongly suggest that virally encoded miRNAs are able to regulate fundamental biological processes such as immune recognition, promotion of cell survival, angiogenesis, proliferation, and cell differentiation. This chapter aims to summarize our current knowledge of viral miRNAs, their targets and function, and the challenges lying ahead to decipher their role in viral biology, pathogenesis, and for gamma-herepsvirus-encoded miRNAs, potentially tumorigenesis.