CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.
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DOI:
10.1016/j.molcel.2014.03.011
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发表时间:
2014-04-24
期刊:
影响因子:
16
通讯作者:
Marraffini, Luciano A.
Marraffini, Luciano A.
中科院分区:
生物学1区
文献类型:
--
作者:
Barrangou, Rodolphe;Marraffini, Luciano A.

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规则间隔短回文重复序列(CRISPR)和相关蛋白(Cas)组成了CRISPR-Cas系统,该系统在许多细菌和大多数古细菌中赋予针对外源因子的适应性免疫。CRISPR介导的免疫是通过从侵入性遗传元件如质粒和病毒中摄取DNA,然后将其整合到CRISPR基因座中而发生的。这些基因座随后被转录并加工成小干扰RNA,其引导核酸酶特异性切割互补序列。从概念上讲,CRISPR-Cas与哺乳动物适应性免疫系统具有相同的功能特征,同时也表现出拉马克进化的特征。由于从外源因子剪接的免疫标记物在CRISPR基因座中迭代整合,它们构成了疫苗接种事件的遗传记录,并反映了环境条件和随时间的变化。Cas内切核酸酶,其可以通过小向导RNA重编程,已经显示出前所未有的潜力和灵活性的基因组编辑,并可以重新用于许多DNA靶向应用,包括转录控制。
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing, and can be repurposed for numerous DNA targeting applications including transcriptional control.
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