放射性RNAアルファベットの化学変異
Alexander R Rovira1, Andrea Fin1, Yitzhak Tor1
1Department of Chemistry and Biochemistry, University of California, San Diego , La Jolla, California 92093-0358, United States.
Journal of the American Chemical Society
|November 3, 2015
まとめ
研究者は,同型ピューリンとピリミジン類のリボヌクレオシドの新型光アルファベットを開発した. これらのアナログは天然のヌクレオシドのように機能し,合成生物学のアプリケーションに改善された機能を提供します.
科学分野:
- 合成生物学
- 核酸化学
- 生物化学
背景:
- 人工核酸システムの開発は 生物学的機能の拡大に不可欠です
- 既存の改造された核酸化物は,安定性や機能性においてしばしば制限に直面する.
- イソチアゾール[4,3-d]ピリミジン誘導体は,ニュクレオシド設計のための新しいヘテロサイクルコアを提供します.
研究 の 目的:
- 進化した光リボヌクレオシドアルファベットと同型ピューリンおよびピリミジンアナログを記述する.
- これらの新しい核酸の構造的および生化学的性質を評価する.
- 既存の改変RNAのアルファベットと 性能を比較する
主な方法:
- 同型ピュリン ((tz) A, (tz) G) とピリミジン ((tz) U, (tz) C) のリボヌクレオシドアナログの合成
- 合成された核酸の構造分析
- 機能的同等性および性能を決定するための生化学的測定.
主要な成果:
- 合成されたヌクレオシド,特にC-ヌクレオシドプーリン類は,天然のヌクレオシドの忠実な同型および同機能の代替物として作用する.
- 新しいアルファベットは,チエノ[3,4-d]ピリミジンから派生したRNAと比較して改善された特徴を示しています.
- 鍵となる窒素原子の復元により, (tz) A上のアデノシンデアミナーゼ活性によって示される同機能的行動が可能である.
結論:
- 記述された光リボヌクレオシドアルファベットは,拡張された遺伝システムのための堅固な,同機能的な構成要素を提供します.
- これらのヌクレオシド類は,以前の改変RNAシステムに比べ,著しい進歩を示しています.
- 設計戦略は,適応した生化学的特性を有する新しいニュクレオシドを作成するための経路を提供します.
関連する概念動画
Spontaneous and Induced Mutations
3.0K
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
3.0K
Mutations in Microorganisms
1.1K
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
1.1K
Mutations
45.5K
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...
45.5K
Mutations
96.4K
Overview
96.4K
RNA Editing
10.2K
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...
10.2K
Mismatch Repair
7.0K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
7.0K


