エクソン結合マイクロアレイによるヒトの代替プレ-mRNAスプライシングに関する全ゲノム調査
Jason M Johnson1, John Castle, Philip Garrett-Engele
1Rosetta Inpharmatics LLC, Merck & Co., Inc., 12040 115th Avenue N.E., Kirkland, WA 98034, USA. jason_johnson@merck.com
まとめ
遺伝子発現の重要なプロセスである代替スプライシングは,ヒトでは広く使用されています. この研究は,人間の遺伝子の少なくとも74%が代替スプライシングを受け,発達や病気に影響を及ぼすことを明らかにしています.
科学分野:
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
- バイオインフォマティックス
背景:
- 代替プリメッセンジャーRNA (プリ-mRNA) のスプライシングは,発達,生理学,および疾患にとって極めて重要です.
- 人間の遺伝子の半分以上は,代替的にスプライスされていることが知られており,その重要性を強調しています.
- 組織と発達段階における代替スプライシングの規制と生物学的役割を理解するには,体系的なアプローチが必要です.
研究 の 目的:
- 大量のヒト遺伝子の間で起こる代替スプライシングイベントを体系的にモニタリングする.
- 代替スプライシングイベントの組織および細胞系分布を決定する.
- 既知および新規の代替スプライシングイベントを特定し,その発生率を定量化します.
主な方法:
- マイクロアレイ技術を活用して,すべてのエクソン-エクソン交差点でのスプライシングを分析しました.
- 10,000以上のマルチエクソンヒト遺伝子を調べました.
- 52種類の多様なヒト組織と細胞系から採取したサンプルを分析した.
主要な成果:
- ゲノム全体のデータを生成し,何千もの代替スプライシングイベントの実験的証拠を提供しました.
- これらのスプライシングイベントの組織および細胞系分布を文書化しました.
- 人間のマルチエクソン遺伝子の少なくとも74%が代替スライスされていることが確認され,これまでの推定を上回る.
結論:
- 代替スプライシングは,ヒトゲノムの普遍的な特徴です.
- 開発されたマイクロアレイアプローチは,代替スプライシングを包括的に研究するための強力なツールを提供します.
- これらの発見は,健康と病気における代替スプライシングの機能的および規制的側面に関するさらなる研究のための基盤を提供します.
関連する概念動画
Mismatch Repair
Overview
pre-mRNA Processing
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Pre-mRNA Processing
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Pre-mRNA Processing: Modification of pre-mRNA Ends
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
Mismatch Repair
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...


