一个进化独特的病毒RdRP表明了原始元素的共同双重功能特征
Hengxia Jia1,2, Shunli Liu1,2, Guibo Rao1
1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, No. 262 Jin Long Street, Wuhan, Hubei 430207, China.
Science advances
|April 18, 2025
概括
来自登革热病毒2和Aspergillus fumigatus polymycovirus-1等病毒的RNA依赖RNA聚合酶 (RdRP) 中的原始元素 (PE) 显示了保存的双重功能. 这种PE的功能性保存超出了序列和结构变异的范围.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 依赖RNA的RNA聚合酶 (RdRPs) 是合成RNA的关键病毒酶.
- 许多病毒RdRP通过de novo启动启动RNA合成,利用一个原始元素 (PE) 和一个原始核酸三酸盐.
- 在登革热病毒2 (DENV2) RdRP中PE的作用包括在从启动到延长的过渡过程中进行重新折叠,通过与上游RNA复合体相互作用来稳定复合体.
研究的目的:
- 研究原始元素 (PE) 在病毒RNA依赖RNA聚合酶 (RdRP) 中保存的功能作用.
- 探索不同病毒家族的PE的结构和功能多样性,特别是检查一个多重病毒.
- 确定在DENV2中观察到的PE的双重功能是否是其他病毒RdRP中保留的特征.
主要方法:
- 来自Aspergillus fumigatus polymycovirus-1 (AfuPmV-1) 的RNA依赖RNA聚合酶 (RdRP) 的晶体结构的分析.
- 在DENV2 RdRP和AfuPmV-1 RdRP中对PE进行比较的结构和功能分析.
- 酶学研究以描述启动和延伸机制.
主要成果:
- 在AfuPmV-1 RdRP晶体结构中观察到一个复杂的PE再折叠机制.
- AfuPmV-1 RdRP代表了正链和双链RNA病毒之间的进化联系.
- 尽管DENV2和AfuPmV-1 RdRP在启动到延长过渡期间在结构细节和酶特征上存在显著差异,但PE始终表现出双重功能.
结论:
- 病毒RNA依赖RNA聚合酶 (RdRP) 中的原始元素 (PE) 在各种病毒家族中表现出功能性保护.
- 在启动和延伸稳定中,PE的这种保留的双重功能超越了序列和结构的变化.
- 这些发现突出了病毒RNA合成的基本机制,适用于广泛的RNA病毒.
相关概念视频
01:10Retrovirus Life Cycles
45.4K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
45.4K
00:57Viral Recombination
23.1K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
23.1K
02:28Leaky Scanning
5.0K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.0K
02:33Retroviruses
12.1K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.1K
02:35RACE - Rapid Amplification of cDNA Ends
6.2K
Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific...
6.2K