METTL3-METTL14複合体によるN(6) -アデノシンメチル化の構造的基礎
Xiang Wang1, Jing Feng1, Yuan Xue1
1National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan 430070, China.
Nature
|June 10, 2016
まとめ
METTL3-METTL14複合体は,N(6) -メチラデノシン (m(6) A部位でRNAをメチル化する. 構造的および生化学的なデータは,METTL3が触媒核であり,METTL14がm(6) A変異のためのRNA結合プラットフォームであることを明らかにする.
科学分野:
- 生物化学
- 分子生物学
- 構造生物学
背景:
- 細胞過程において,N(6) メチラデノシン (m(6) AのようなRNAの化学的変異は極めて重要です.
- m(6) A変異は,RNAメチルトランスファーゼ (MTases) とデメチラーゼによって動的に調節される.
- メチルトランスフェラーゼ型3 (METTL3) - メチルトランスフェラーゼ型14 (METTL14) 複合体は,主要なメチルトランスフェラーゼである.
研究 の 目的:
- メチルトランスフェラーゼ複合体内のMETTL3とMETTL14の異なる役割を明らかにする.
- METTL3-METTL14複合体の触媒活動と基板認識の構造的基礎を決定する.
主な方法:
- METTL3-METTL14ヘテロダイマーの高解像度構造を取得するために,X線結晶学を使用した.
- 構造は,リガンドフリー状態,S- アデノシルメチオニン (AdoMet) 結合状態,S- アデノシルホモシステイン (AdoHcy) 結合状態で決定された.
- 構造的発見を裏付けるために生化学的分析が行われました.
主要な成果:
- 結晶構造は,METTL3とMETTL14の両方がクラスI MTaseの折りたたみを持ち,水素結合を通じて相互作用し,正電荷の溝を形成することを明らかにした.
- S- アデノシルメチオニン (AdoMet) は,METTL3の活性部位においてのみ観察され,METTL14では観察されなかった.
- 生物化学的データによると,METTL3は触媒成分として機能し,METTL14はRNA結合プラットフォームとして機能する.
結論:
- METTL3-METTL14複合体は,特殊な役割で機能する.METTL3は触媒核であり,METTL14はRNA結合プラットフォームである.
- この構造的および機能的洞察は,変更とその規制を理解するための枠組みを提供します.
- 発見は,DNAのN(6) -アデニンMTasesに類似した標的認識メカニズムを強調しています.
関連する概念動画
01:17Phase II Reactions: Methylation Reactions
860
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
860
01:28Biosynthesis of Nucleic Acids
1.5K
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
1.5K
02:23RNA Editing
10.1K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
10.1K
02:36Transfer RNA Synthesis
13.7K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
13.7K
01:25Nucleic Acid Structure
10.0K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
10.0K
01:23RNA Structure
80.1K
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
80.1K