CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III.

CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III.
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通过反式编码的小 RNA 和宿主因子 RNase III 进行 CRISPR RNA 成熟。

DOI:
10.1038/nature09886
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发表时间:
2011-03-31
期刊:
影响因子:
64.8
通讯作者:
Charpentier, Emmanuelle
Charpentier, Emmanuelle
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Deltcheva, Elitza;Chylinski, Krzysztof;Sharma, Cynthia M.;Gonzales, Karine;Chao, Yanjie;Pirzada, Zaid A.;Eckert, Maria R.;Vogel, Joerg;Charpentier, Emmanuelle

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CRISPR/Cas系统构成了一类广泛的免疫系统,其保护细菌和古细菌免受细菌和质粒的侵害,并且通常使用重复/间隔子衍生的短crRNA以序列特异性方式沉默外源核酸。尽管crRNA的成熟代表了CRISPR激活中的关键事件,但在许多CRISPR/Cas亚型中缺少负责的核糖核酸内切酶(CasE、Cas 6、Csy 4)。在这里,人类病原体化脓性链球菌的差异RNA测序发现了tracrRNA,这是一种与crRNA前体转录物的重复区域具有24个核苷酸互补性的反式编码小RNA。我们发现,tracrRNA通过广泛保守的内源性RNase III和CRISPR相关的Csn 1蛋白的活性指导crRNA的成熟;所有这些组分对于保护S.化脓性链球菌对原噬菌体衍生的DNA。我们的研究揭示了小向导RNA成熟的新途径,以及细菌RNA介导的针对入侵者的免疫所需的宿主因子(RNase III)的第一个例子。
CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24 nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.
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