人間のカテキル-O-メチルトランスフェラーゼハプロタイプは,mRNA二次構造を変更することによってタンパク質発現を調節する
A G Nackley1, S A Shabalina, I E Tchivileva
1Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC 27599, USA.
まとめ
Catechol-O-methyltransferase (COMT) 遺伝子の同名の変異は,タンパク質のレベルと活性に影響を与え,痛みに対する感受性に影響を与えます. 単一のSNPではなくハプロタイプが,COMT遺伝子の機能を理解するために重要である.
科学分野:
- 遺伝学 遺伝学とは
- 分子生物学は分子生物学である.
- 神経科学は神経科学である.
背景:
- カテコル-O-メチルトランスフェラーゼ (COMT) は,神経伝達物質のレベルを調節する上で重要な役割を果たします.
- COMTの活動は,痛み知覚,認知機能,気分調節に関与しています.
- COMT遺伝子の遺伝的変異は,その酵素活性および関連する機能に影響を与える可能性があります.
研究 の 目的:
- 共通するCOMT遺伝子ハプロタイプがCOMT酵素活性に及ぼす機能的影響を調査する.
- COMTハプロタイプ内の同名および非同名変異の役割を決定する.
- メッセンジャーRNA構造とタンパク質発現レベルとの関係を調査する.
主な方法:
- 3つの一般的なヒトCOMT遺伝子ハプロタイプの分析.
- ハプロタイプ間のCOMT酵素活性差異の評価.
- メッセンジャーRNAの局所的な幹ループ構造の調査.
- サイト指向型変異は,RNAの構造を変化させる.
主要な成果:
- 同義的な変化を持つハプロタイプは,COMTの酵素活性において最も顕著な違いを示した.
- より安定したメッセンジャーRNA幹ループ構造を持つハプロタイプでは,翻訳タンパク質のレベルが低下することが観察されました.
- タンパク質のレベルと活性の回復は,ミュータゲネシスによる安定したRNA構造の破壊によって達成されました.
結論:
- 同義的な遺伝的変異は,タンパク質のレベルと活動に実質的な機能的な影響を与える可能性があります.
- メッセンジャーRNA二次構造は,COMTタンパク質発現を調節する上で重要な役割を果たします.
- シングル・ヌクレオチド・ポリモルフィズム分析よりもハプロタイプ分析は,COMT遺伝子変異の包括的な理解のために不可欠です.
関連する概念動画
Mutations
Overview
Transfer RNA Synthesis
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...
RNA Editing
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...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
What is Gene Expression?
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...


