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研究发现CRISPR转录的关键抑制因子
作者:小柯机器人 发布时间:2019/9/6 14:14:30

加拿大多伦多大学Alan R. Davidson课题组发现,抗CRISPR相关蛋白是抗CRISPR转录的关键抑制因子。该研究2019年9月5日发表在《细胞》上。

他们揭示了抗CRISPR蛋白(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,并且抗CRISPR相关基因(aca)蛋白随后抑制该转录。没有aca活性,这种转录对噬菌体是致死的。研究证明,在感染过程中积累足够量的Acr蛋白,可抑制宿主细胞中现有的CRISPR-Cas复合物。aca蛋白的保守作用,或减轻Acr启动子转录的有害作用。

据介绍, 噬菌体表达抗CRISPR(Acr)蛋白,抑制原本会破坏其基因组的CRISPR-Cas系统。大多数Acr基因位于抗CRISPR相关基因附近,其编码具有螺旋-转角-螺旋DNA结合基序的蛋白质。aca基因的保守性已成为鉴定Acr基因的标志,但尚未研究这些基因编码的蛋白质的功能。

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

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/