研究發現CRISPR轉錄的關鍵抑制因子
作者：
小柯機器人發布時間：2019/9/6 14:14:30
加拿大多倫多大學Alan R. Davidson課題組發現，抗CRISPR相關蛋白是抗CRISPR轉錄的關鍵抑制因子。該研究2019年9月5日發表在《細胞》上。
他們揭示了抗CRISPR蛋白（Acr）相關啟動子，在噬菌體DNA注射後立即驅動高水平的Acr轉錄，並且抗CRISPR相關基因（aca）蛋白隨後抑制該轉錄。沒有aca活性，這種轉錄對噬菌體是致死的。研究證明，在感染過程中積累足夠量的Acr蛋白，可抑制宿主細胞中現有的CRISPR-Cas複合物。aca蛋白的保守作用，或減輕Acr啟動子轉錄的有害作用。
據介紹， 噬菌體表達抗CRISPR（Acr）蛋白，抑制原本會破壞其基因組的CRISPR-Cas系統。大多數Acr基因位於抗CRISPR相關基因附近，其編碼具有螺旋-轉角-螺旋DNA結合基序的蛋白質。aca基因的保守性已成為鑑定Acr基因的標誌，但尚未研究這些基因編碼的蛋白質的功能。
附：英文原文
Title: Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription
Author: Sabrina Y. Stanley, Adair L. Borges, Kuei-Ho Chen, Danielle L. Swaney, Nevan J. Krogan, Joseph Bondy-Denomy, Alan R. Davidson
Issue&Volume: Volume 178 Issue 6
Abstract: 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.
DOI: 10.1016/j.cell.2019.07.046
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30846-3
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