How the Replication and Transcription Complex Functions in Jumping Transcription of SARS-CoV-2.
How the Replication and Transcription Complex Functions in Jumping Transcription of SARS-CoV-2.
复制标题
复制和转录复合体如何在 SARS-CoV-2 跳跃转录中发挥作用
DOI：
10.3389/fgene.2022.904513
复制
发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
背景：冠状病毒病2019 （COVID-19）是由严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起的。尽管正在进行前所未有的努力来开发针对这种疾病的治疗策略，但科学家们对冠状病毒复制和转录复合体（RTC）的结构和功能知之甚少。确定所有RTC组分及其排列是最终确定其整体结构，从而在分子水平上完全了解其所有功能的必要步骤。结果：主要结果包括：1)含有典型和非典型NSP15切割基序的发夹是典型和非典型转录调控序列（TRS）发夹；2) TRS发夹可用于鉴定冠状病毒基因组中的重组区；3) RNA甲基化通过影响碱基配对的形成参与了冠状病毒局部RNA结构的确定；4) CoV RTC整体结构的最终确定需要在实验设计中考虑METTL3。结论：在本研究中，我们提出了NSP12-15和METTL3在RTC全局结构中的理论排列，并构建了RTC在冠状病毒跳跃转录中的作用模型。作为最重要的发现，TRS发夹首次在分子水平上解释了冠状病毒的NSP15切割、RNA甲基化及其关联。我们的发现丰富了基因表达及其调控领域的基础知识，为今后的研究提供了重要的基础。
Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC). Ascertaining all the RTC components and the arrangement of them is an indispensably step for the eventual determination of its global structure, leading to completely understanding all of its functions at the molecular level. Results: The main results include: 1) hairpins containing the canonical and non-canonical NSP15 cleavage motifs are canonical and non-canonical transcription regulatory sequence (TRS) hairpins; 2) TRS hairpins can be used to identify recombination regions in CoV genomes; 3) RNA methylation participates in the determination of the local RNA structures in CoVs by affecting the formation of base pairing; and 4) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Conclusions: In the present study, we proposed the theoretical arrangement of NSP12-15 and METTL3 in the global RTC structure and constructed a model to answer how the RTC functions in the jumping transcription of CoVs. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.
影响因子：
3.5
作者：
Liu C;Chen Z;Hu Y;Ji H;Yu D;Shen W;Li S;Ruan J;Bu W;Gao S
通讯作者：
Gao S