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小干扰RNA、微小RNA与人类免疫缺陷病毒:前景与挑战

siRNA, miRNA and HIV: promises and challenges.

作者信息

Yeung Man Lung, Bennasser Yamina, LE Shu Yun, Jeang Kuan Teh

机构信息

National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892-0460, USA.

出版信息

Cell Res. 2005 Nov-Dec;15(11-12):935-46. doi: 10.1038/sj.cr.7290371.

DOI:10.1038/sj.cr.7290371
PMID:16354572
Abstract

Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 (HIV-1) which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi (RNA interference). On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells' antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs (vmiRNAs).

摘要

小干扰RNA(siRNA)和微小RNA(miRNA)是长度为18 - 25个核苷酸(nt)的小RNA,在调节基因表达中发挥重要作用。它们被整合到RNA诱导沉默复合体(RISC)中,并基于互补碱基配对作为沉默其相应靶mRNA的向导。基因沉默的前景使许多研究人员将siRNA视为一种抗病毒工具。然而,在长期情况下,许多病毒似乎能够逃避这种治疗策略。人类免疫缺陷病毒1型(HIV - 1)就是一个例子,它能够通过突变siRNA靶向序列或编码RNAi(RNA干扰)的部分抑制因子来逃避RNA沉默。另一方面,由于miRNA靶向不需要碱基配对的绝对互补性,病毒通过突变逃避miRNA介导的沉默可能更难实现。在这篇综述中,我们讨论了各种病毒用于逃避细胞抗病毒si/mi - RNA防御的策略,以及病毒如何通过编码病毒miRNA(vmiRNA)来控制和调节宿主细胞基因的相关概念。

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