抗 CRISPR 相关蛋白是抗 CRISPR 转录的关键抑制剂。
Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription.
机构信息
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Cell. 2019 Sep 5;178(6):1452-1464.e13. doi: 10.1016/j.cell.2019.07.046. Epub 2019 Aug 29.
Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of acr transcription immediately after phage DNA injection and that Aca proteins subsequently repress this transcription. Without Aca activity, this strong transcription is lethal to a phage. Our results demonstrate how sufficient levels of Acr proteins accumulate early in the infection process to inhibit existing CRISPR-Cas complexes in the host cell. They also imply that the conserved role of Aca proteins is to mitigate the deleterious effects of strong constitutive transcription from acr promoters.
噬菌体表达抗 CRISPR（Acr）蛋白以抑制 CRISPR-Cas 系统，否则这些系统会破坏它们的基因组。大多数 acr 基因位于抗 CRISPR 相关（aca）基因附近，这些基因编码具有螺旋-转角-螺旋 DNA 结合模体的蛋白。aca 基因的保守性一直是鉴定 acr 基因的标志，但这些基因编码的蛋白的功能尚未被研究。在这里，我们揭示了 acr 相关启动子在噬菌体 DNA 注射后立即驱动高水平的 acr 转录，而 Aca 蛋白随后抑制这种转录。如果没有 Aca 活性，这种强烈的转录对噬菌体是致命的。我们的结果表明，在感染过程的早期，Acr 蛋白如何积累到足够的水平来抑制宿主细胞中现有的 CRISPR-Cas 复合物。它们还暗示 Aca 蛋白的保守作用是减轻 acr 启动子强组成型转录的有害影响。
Zotero 插件