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Modified base-binding EVE and DCD domains: striking diversity of genomic contexts in prokaryotes and predicted involvement in a variety of cellular processes
BMC Biology ( IF 5.4 ) Pub Date : 2020-11-04 , DOI: 10.1186/s12915-020-00885-2
Ryan T Bell 1 , Yuri I Wolf 1 , Eugene V Koonin 1
Affiliation  

DNA and RNA of all cellular life forms and many viruses contain an expansive repertoire of modified bases. The modified bases play diverse biological roles that include both regulation of transcription and translation, and protection against restriction endonucleases and antibiotics. Modified bases are often recognized by dedicated protein domains. However, the elaborate networks of interactions and processes mediated by modified bases are far from being completely understood. We present a comprehensive census and classification of EVE domains that belong to the PUA/ASCH domain superfamily and bind various modified bases in DNA and RNA. We employ the “guilt by association” approach to make functional inferences from comparative analysis of bacterial and archaeal genomes, based on the distribution and associations of EVE domains in (predicted) operons and functional networks of genes. Prokaryotes encode two classes of EVE domain proteins, slow-evolving and fast-evolving ones. Slow-evolving EVE domains in α-proteobacteria are embedded in conserved operons, potentially involved in coupling between translation and respiration, cytochrome c biogenesis in particular, via binding 5-methylcytosine in tRNAs. In β- and γ-proteobacteria, the conserved associations implicate the EVE domains in the coordination of cell division, biofilm formation, and global transcriptional regulation by non-coding 6S small RNAs, which are potentially modified and bound by the EVE domains. In eukaryotes, the EVE domain-containing THYN1-like proteins have been reported to inhibit PCD and regulate the cell cycle, potentially, via binding 5-methylcytosine and its derivatives in DNA and/or RNA. We hypothesize that the link between PCD and cytochrome c was inherited from the α-proteobacterial and proto-mitochondrial endosymbiont and, unexpectedly, could involve modified base recognition by EVE domains. Fast-evolving EVE domains are typically embedded in defense contexts, including toxin-antitoxin modules and type IV restriction systems, suggesting roles in the recognition of modified bases in invading DNA molecules and targeting them for restriction. We additionally identified EVE-like prokaryotic Development and Cell Death (DCD) domains that are also implicated in defense functions including PCD. This function was inherited by eukaryotes, but in animals, the DCD proteins apparently were displaced by the extended Tudor family proteins, whose partnership with Piwi-related Argonautes became the centerpiece of the Piwi-interacting RNA (piRNA) system. Recognition of modified bases in DNA and RNA by EVE-like domains appears to be an important, but until now, under-appreciated, common denominator in a variety of processes including PCD, cell cycle control, antivirus immunity, stress response, and germline development in animals.

中文翻译:

修饰的结合碱基的EVE和DCD域:在原核生物中达到惊人的基因组背景,并预测参与多种细胞过程

所有细胞生命形式的DNA和RNA以及许多病毒都包含大量的修饰碱基。修饰的碱基起着多种生物学作用,包括调节转录和翻译,以及针对限制性核酸内切酶和抗生素的保护。修饰的碱基通常被专用的蛋白质结构域识别。但是,由修饰的碱基介导的相互作用和过程的复杂网络远未完全被理解。我们提出了属于PUA / ASCH域超家族并结合DNA和RNA中各种修饰碱基的EVE域的全面普查和分类。我们采用“内gui关联”方法从细菌和古细菌基因组的比较分析中进行功能推断,基于(预测的)操纵子和基因功能网络中EVE域的分布和关联。原核生物编码两类EVE结构域蛋白,即缓慢进化的蛋白质和快速进化的蛋白质。α-变形杆菌中缓慢发展的EVE结构域嵌入保守的操纵子中,可能通过与tRNA中的5-甲基胞嘧啶结合,参与翻译和呼吸作用的耦合,尤其是细胞色素C的生物发生。在β和γ变形杆菌中,保守的关联通过非编码6S小RNA暗示EVE结构域参与细胞分裂,生物膜形成和全局转录调控,这可能被EVE结构域修饰和结合。在真核生物中,据报道,含有EVE域的THYN1样蛋白可抑制PCD并调节细胞周期,通过结合5-甲基胞嘧啶及其衍生物在DNA和/或RNA。我们假设PCD和细胞色素c之间的联系是从α-proteobacterial和线粒体原生内共生体继承的,并且出乎意料的是,可能涉及EVE域对碱基识别的修饰。快速发展的EVE域通常嵌入防御环境中,包括毒素-抗毒素模块和IV型限制系统,这提示了在入侵DNA分子中识别修饰碱基并以限制为目标时的作用。我们还确定了类似EVE的原核发育和细胞死亡(DCD)域,这些域也与包括PCD在内的防御功能有关。该功能由真核生物继承,但在动物中,DCD蛋白显然被延伸的Tudor家族蛋白取代,其与Piwi相关的Argonautes的合作关系成为Piwi相互作用RNA(piRNA)系统的核心。通过EVE样域识别DNA和RNA中修饰的碱基似乎很重要,但直到现在,在PCD,细胞周期控制,抗病毒免疫,应激反应和种系发育等多种过程中,人们的价值均未得到充分认识。在动物中。
更新日期:2020-11-04
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