The 3' untranslated regions of influenza genomic sequences are 5'PPP-independent ligands for RIG-I.
The 3' untranslated regions of influenza genomic sequences are 5'PPP-independent ligands for RIG-I.
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DOI：
10.1371/journal.pone.0032661
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sambhara S
中科院分区：
文献类型：
--
作者：
Davis WG;Bowzard JB;Sharma SD;Wiens ME;Ranjan P;Gangappa S;Stuchlik O;Pohl J;Donis RO;Katz JM;Cameron CE;Fujita T;Sambhara S
视黄酸诱导基因i （RIG-I）是抗病毒免疫的关键调控因子。RIG-I通常被认为是由含有5 ' -三磷酸（PPP）基团的ssRNA或长度为~ 300 bp的未磷酸化dsRNA激活的。然而，目前尚不清楚长度、核苷酸序列、二级结构和5 '端修饰的变化如何影响这些配体结合和激活RIG-I的能力。为了在自然存在的配体背景下进一步研究这些参数，我们检测了来自流感病毒NS1基因片段的5 ‘和3 ’非翻译区（UTR）的RNA序列。正如预期的那样，rig - i依赖性干扰素-β (IFN-β)由流感cRNA的5 ' UTR序列或其补体（长度为26 nt）诱导，需要5 ' ppp组的存在。相比之下，3 ' UTR cRNA序列或其补体（172 nt）对RIG-I的激活仅表现出部分5 ‘ ppp依赖性，因为覆盖5 ’端或用CIP处理显示RIG-I激活的适度降低。此外，3 ' UTR内一个较小的、U/ a丰富的区域对IFN-β的诱导完全不依赖于5 ' ppp。我们的研究结果表明，RNA序列、长度和二级结构都决定了rig - 1诱导干扰素是否需要5'PPP片段。
Retinoic acid inducible gene-I (RIG-I) is a key regulator of antiviral immunity. RIG-I is generally thought to be activated by ssRNA species containing a 5′-triphosphate (PPP) group or by unphosphorylated dsRNA up to ∼300 bp in length. However, it is not yet clear how changes in the length, nucleotide sequence, secondary structure, and 5′ end modification affect the abilities of these ligands to bind and activate RIG-I. To further investigate these parameters in the context of naturally occurring ligands, we examined RNA sequences derived from the 5′ and 3′ untranslated regions (UTR) of the influenza virus NS1 gene segment. As expected, RIG-I-dependent interferon-β (IFN-β) induction by sequences from the 5′ UTR of the influenza cRNA or its complement (26 nt in length) required the presence of a 5′PPP group. In contrast, activation of RIG-I by the 3′ UTR cRNA sequence or its complement (172 nt) exhibited only a partial 5′PPP-dependence, as capping the 5′ end or treatment with CIP showed a modest reduction in RIG-I activation. Furthermore, induction of IFN-β by a smaller, U/A-rich region within the 3′ UTR was completely 5′PPP-independent. Our findings demonstrated that RNA sequence, length, and secondary structure all contributed to whether or not the 5′PPP moiety is needed for interferon induction by RIG-I.
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