Cyclic oligoadenylate signalling and regulation by ring nucleases during type III CRISPR defence.

Cyclic oligoadenylate signalling and regulation by ring nucleases during type III CRISPR defence.
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DOI:
10.1261/rna.078739.121
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发表时间:
2021-05-13
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
White MF
White MF
中科院分区:
其他
文献类型:
--
作者:
Athukoralage JS;White MF

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在原核生物中,CRISPR-Cas免疫系统识别并切割外来核酸以防御移动的遗传元件(MGE)。III型CRISPR-Cas复合物还合成环状寡腺苷酸(cOA)第二信使,其激活参与抗病毒防御的CRISPR辅助蛋白。特别是,cOA刺激的核酸酶非特异性地降解RNA和DNA,这减慢了MGE复制,但也阻碍了细胞生长,需要消除cOA的机制以促进细胞恢复。现存的cOA被一类称为“环状核酸酶”的新型酶降解,该酶特异性切割cOA并关闭CRISPR辅助酶。迄今为止,已经表征了几个环核酸酶家族,包括MGE用于规避CRISPR免疫的家族,并且包括不同的蛋白质折叠和不同的cOA切割机制。在这篇综述中,我们研究了cOA信号,讨论了不同的环核酸酶如何调节cOA信号通路,并反映了基于环核苷酸的免疫系统之间的相似之处,以揭示新的探索领域。
In prokaryotes, CRISPR-Cas immune systems recognize and cleave foreign nucleic acids to defend against mobile genetic elements (MGEs). Type III CRISPR-Cas complexes also synthesize cyclic oligoadenylate (cOA) second messengers, which activate CRISPR ancillary proteins involved in antiviral defense. In particular, cOA-stimulated nucleases degrade RNA and DNA nonspecifically, which slows MGE replication but also impedes cell growth, necessitating mechanisms to eliminate cOA in order to facilitate cell recovery. Extant cOA is degraded by a new class of enzyme termed a “ring nuclease,” which cleaves cOA specifically and switches off CRISPR ancillary enzymes. Several ring nuclease families have been characterized to date, including a family used by MGEs to circumvent CRISPR immunity, and encompass diverse protein folds and distinct cOA cleavage mechanisms. In this review we examine cOA signaling, discuss how different ring nucleases regulate the cOA signaling pathway, and reflect on parallels between cyclic nucleotide-based immune systems to reveal new areas for exploration.
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