m6 RNAのメチル化は内生レトロウイルスの運命を調節する
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
まとめ
N-メチラデノシン (m6A) RNAメチレーションは,ERV mRNAの安定性を低下させ,内生レトロウイルス (ERV) を制限する. このRNA改変プロセスは,潜在的に有害なレトロウイルスRNA種を除去することによって,細胞の完全性を維持するために不可欠です.
科学分野:
- 分子生物学
- 遺伝学
- エピジェネティクス
背景:
- 内生レトロウイルス (ERV) は,ゲノム調節と細胞生理に影響を与える統合レトロウイルス配列である.
- ERVを抑制できないと がん,不妊症,老化,神経変性などの病気に繋がります
研究 の 目的:
- 内生レトロウイルス (ERV) を抑制するメカニズムを特定する.
- ERV 調節における m6A RNA メチル化の役割を調査する.
主な方法:
- ネズミの胚性幹細胞における ゲノムスケール CRISPR ノックアウトスクリーン
- m6Aメチルトランスフェラーゼ複合体 (METTL3-METTL14) の枯渇時にmRNAの豊富さとタンパク質のレベルを分析する.
- クロマチンの状態とmRNAの安定性のモニタリング
主要な成果:
- m6ARNAメチレーションはERVを制限し,特に内A粒子 (IAP) とERVK要素を標的にする.
- METTL3- METTL14複合体の枯渇は,IAP mRNAとタンパク質の豊富さを増加させる.
- メチル化により,主にYTHDF読者タンパク質を通じてIAP mRNAの半減期が短縮される.
結論:
- RNAメチル化,特にm6Aは,反応性ERV由来RNA種に対する保護メカニズムとして作用する.
- このRNAの改変は,細胞の完全性を維持するために不可欠であり,特に転写サイレンシングが効果的でない場合です.
関連する概念動画
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


