Small CRISPR RNAs guide antiviral defense in prokaryotes.

Small CRISPR RNAs guide antiviral defense in prokaryotes.
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DOI:
10.1126/science.1159689
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发表时间:
2008-08-15
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
van der Oost J
van der Oost J
中科院分区:
其他
文献类型:
--
作者:
Brouns SJ;Jore MM;Lundgren M;Westra ER;Slijkhuis RJ;Snijders AP;Dickman MJ;Makarova KS;Koonin EV;van der Oost J

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原核生物通过将病毒核酸的短片段整合到成簇的规律间隔的短回文重复序列(CRISPR)中获得病毒抗性。在此我们展示了宿主的CRISPR相关(Cas)蛋白如何利用CRISPR中包含的病毒衍生序列来介导一种抗病毒反应以抵抗感染。在CRISPR转录之后,一种被称为Cascade的Cas蛋白复合物在每个重复序列处切割CRISPR RNA前体,并保留含有病毒衍生序列的切割产物。在解旋酶Cas3的协助下,这些成熟的CRISPR RNA随后作为小引导RNA,使Cascade能够干扰病毒增殖。我们的研究结果表明,由Cascade的CRISPR RNA核酸内切酶亚基形成成熟的引导RNA是抗病毒防御的一种机制要求。
Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
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