Bacterial defense amplification Prokaryotic type III CRISPR systems use the effector complex and additional proteins such as Csm6 to destroy both the genome and the transcripts of invaders. However, how the effector complex and Csm6 coordinate CRISPR activity remains a mystery. Kazlauskiene et al. found that a cyclic oligonucleotide–based signaling pathway can regulate the defense response (see the Perspective by Amitai and Sorek). Upon target recognition, the Cas10 subunit of the effector complex synthesizes cyclic oligoadenylates, which act as second messengers to initiate and amplify the nuclease activity of Csm6. Science, this issue p. 605; see also p. 550 Cyclic oligoadenylates are signaling molecules that regulate type III-A CRISPR systems to provide full antiviral immunity in bacteria. Type III CRISPR-Cas systems in prokaryotes provide immunity against invading nucleic acids through the coordinated degradation of transcriptionally active DNA and its transcripts by the Csm effector complex. The Cas10 subunit of the complex contains an HD nuclease domain that is responsible for DNA degradation and two Palm domains with elusive functions. In addition, Csm6, a ribonuclease that is not part of the complex, is also required to provide full immunity. We show here that target RNA binding by the Csm effector complex of Streptococcus thermophilus triggers Cas10 to synthesize cyclic oligoadenylates (cAn; n = 2 to 6) by means of the Palm domains. Acting as signaling molecules, cyclic oligoadenylates bind Csm6 to activate its nonspecific RNA degradation. This cyclic oligoadenylate–based signaling pathway coordinates different components of CRISPR-Cas to prevent phage infection and propagation.

中文翻译：

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III型CRISPR-Cas系统中的环状寡核苷酸信号通路

细菌防御扩增原核 III 型 CRISPR 系统使用效应复合物和其他蛋白质（如 Csm6）来破坏入侵者的基因组和转录物。然而，效应复合物和 Csm6 如何协调 CRISPR 活动仍然是个谜。Kazlauskiene 等。发现基于环状寡核苷酸的信号通路可以调节防御反应（参见 Amitai 和 Sorek 的观点）。在目标识别后，效应复合物的 Cas10 亚基合成环状寡腺苷酸，作为第二信使启动和放大 Csm6 的核酸酶活性。科学，这个问题 p。605; 另见第。550 环状寡腺苷酸是信号分子，可调节 III-A 型 CRISPR 系统以在细菌中提供完整的抗病毒免疫。原核生物中的 III 型 CRISPR-Cas 系统通过 Csm 效应复合物对转录活性 DNA 及其转录物的协调降解，提供针对入侵核酸的免疫力。该复合物的 Cas10 亚基包含一个负责 DNA 降解的 HD 核酸酶域和两个具有难以捉摸的功能的 Palm 域。此外，Csm6 是一种不属于复合物的核糖核酸酶，也需要提供完全免疫。我们在这里展示了通过嗜热链球菌的 Csm 效应复合物结合目标 RNA，触发 Cas10 通过 Palm 结构域合成环状寡聚腺苷酸（cAn；n = 2 到 6）。作为信号分子，环状寡腺苷酸结合 Csm6 以激活其非特异性 RNA 降解。