Self-targeting by CRISPR: gene regulation or autoimmunity?

Self-targeting by CRISPR: gene regulation or autoimmunity?
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DOI:
10.1016/j.tig.2010.05.008
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发表时间:
2010-08
期刊:
影响因子:
11.4
通讯作者:
Sorek, Rotem
Sorek, Rotem
中科院分区:
生物学1区
文献类型:
--
作者:
Stern, Adi;Keren, Leeat;Wurtzel, Omri;Amitai, Gil;Sorek, Rotem

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CRISPR/Cas是最近发现的一种原核免疫系统,它基于限制噬菌体和质粒感染的小rna(“间隔物”)。据推测,crispr也可以通过利用靶向自身基因的间隔物来调节自身基因的表达。通过分析330个生物体的crispr,我们发现每250个间隔中就有一个是自我靶向的,而这种自我靶向发生在18%的携带crispr的生物体中。然而,物种间完全缺乏保守性,加上自我靶向间隔序列附近大量降解重复序列,表明自我靶向是自身免疫的结果,而不是基因调控。我们提出,CRISPR偶然结合自身核酸会产生自身免疫适应性成本,这可能解释了原核生物中大量降解的CRISPR系统。
CRISPR/Cas is a recently discovered prokaryotic immune system, which is based on small RNAs (“spacers”) that restrict phage and plasmid infection. It has been hypothesized that CRISPRs can also regulate self gene expression by utilizing spacers that target self genes. By analyzing CRISPRs from 330 organisms we found that one in every 250 spacers is self targeting, and that such self-targeting occurs in 18% of all CRISPR-bearing organisms. However, complete lack of conservation across species, combined with abundance of degraded repeats near self-targeting spacers, suggests that self-targeting is a consequence of autoimmunity rather than gene regulation. We propose that accidental incorporation of self nucleic-acids by CRISPR can incur an autoimmune fitness cost, which may explain the abundance of degraded CRISPR systems across prokaryotes.
DOI: 10.1126/science.1165771
发表时间: 2008-12-19
期刊: Science (New York, N.Y.)
影响因子: --
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