CRISPR and Archaea Biology Research Centre, Microbial Technology Institute and State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, P. R. China.
Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit, Paris, 75015, France.
Nucleic Acids Res. 2023 Feb 28;51(4):1707-1723. doi: 10.1093/nar/gkad006.
Cell cycle regulation is of paramount importance for all forms of life. Here, we report that a conserved and essential cell cycle-specific transcription factor (designated as aCcr1) and its viral homologs control cell division in Sulfolobales. We show that the transcription level of accr1 reaches peak during active cell division (D-phase) subsequent to the expression of CdvA, an archaea-specific cell division protein. Cells over-expressing the 58-aa-long RHH (ribbon-helix-helix) family cellular transcription factor as well as the homologs encoded by large spindle-shaped viruses Acidianus two-tailed virus (ATV) and Sulfolobus monocaudavirus 3 (SMV3) display significant growth retardation and cell division failure, manifesting as enlarged cells with multiple chromosomes. aCcr1 over-expression results in downregulation of 17 genes (>4-fold), including cdvA. A conserved motif, aCcr1-box, located between the TATA-binding box and the translation initiation site of 13 out of the 17 highly repressed genes, is critical for aCcr1 binding. The aCcr1-box is present in the promoters and 5' UTRs of cdvA genes across Sulfolobales, suggesting that aCcr1-mediated cdvA repression is an evolutionarily conserved mechanism by which archaeal cells dictate cytokinesis progression, whereas their viruses take advantage of this mechanism to manipulate the host cell cycle.
细胞周期调控对于所有生命形式都至关重要。在这里，我们报告称，一种保守且必需的细胞周期特异性转录因子（命名为 aCcr1）及其病毒同源物控制 Sulfolobales 中的细胞分裂。我们表明，在活跃的细胞分裂（D 期）后，accr1 的转录水平达到峰值，随后是 CdvA 的表达，CdvA 是一种古菌特异性细胞分裂蛋白。过度表达 58-aa 长的 RHH（螺旋-环-螺旋）家族细胞转录因子及其编码的大纺锤形病毒 Acidianus two-tailed virus (ATV) 和 Sulfolobus monocaudavirus 3 (SMV3) 的同源物的细胞表现出明显的生长迟缓和细胞分裂失败，表现为具有多个染色体的增大细胞。aCcr1 的过表达导致 17 个基因（>4 倍）下调，包括 cdvA。一个保守的基序，aCcr1-box，位于 13 个高度受抑制基因的 TATA 结合盒和翻译起始位点之间，对于 aCcr1 结合至关重要。aCcr1-box 存在于 Sulfolobales 中所有 cdvA 基因的启动子和 5'UTR 中，表明 aCcr1 介导的 cdvA 抑制是一种进化上保守的机制，通过该机制，古菌细胞控制胞质分裂的进展，而它们的病毒则利用这种机制来操纵宿主细胞周期。
