一个RNA甲基化调节内源性逆转录病毒的命运
Tomasz Chelmicki1, Emeline Roger2, Aurélie Teissandier2
1Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France. tomasz.chelmicki@curie.fr.
Nature
|January 14, 2021
概括
通过降低ERVmRNA的稳定性来限制内源逆转录病毒 (ERVs). 通过清除可能有害的逆转录病毒RNA物种,这种RNA修饰过程对维持细胞完整性至关重要.
科学领域:
- 分子生物学
- 遗传学
- 表观遗传学
背景情况:
- 内生逆转录病毒 (ERV) 是影响基因组调节和细胞生理的综合逆转录病毒序列.
- 不能抑制ERV与癌症,不孕症,衰老和神经退行等疾病有关.
研究的目的:
- 确定限制内源逆转录病毒 (ERV) 的机制.
- 研究m6ARNA甲基化在ERV调节中的作用.
主要方法:
- 在小鼠胚胎干细胞中进行基因组规模的CRISPR淘汰查.
- 在甲基转移酶复合体 (METTL3-METTL14) 耗尽时分析mRNA丰度和蛋白质水平.
- 对染色质状态和mRNA稳定性的监测.
主要成果:
- m6 ARNA甲基化限制了ERVs,特别是针对内A粒子 (IAP) 和ERVK元素.
- 减少METTL3- METTL14复合体会增加IAP mRNA和蛋白质的丰度.
- 甲基化主要通过YTHDF读者蛋白减少IAPmRNA的半衰期.
结论:
- RNA甲基化,特别是m6A,作为对反应性ERV衍生的RNA物种的保护机制.
- 这种RNA修饰对于维持细胞完整性至关重要,特别是当转录沉默效果较低时.
相关概念视频
Viruses with RNA Genomes
416
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
416
Retroviruses
13.6K
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’...
13.6K
Retrovirus Life Cycles
48.4K
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...
48.4K
Non-LTR Retrotransposons
12.6K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.6K
Size and Structure of Viral Genomes
420
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
420
RNA Stability
34.9K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
34.9K


