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マイクロプロセッサーのバイオゲネシスのステップ miR-17∼92 表現を制御する
Peng Du1, Longfei Wang2, Piotr Sliz3
1Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 11, 2015
まとめ
胚性幹細胞の分化により,miR-17∼92マイクロRNA (miRNA) の発現が動的に調節される. このクラスタからの特定のmiRNAの処理と発現を制御する主要な中間体であるプロゲニターmiRNA (pro- miRNA) がある.
科学分野:
- 分子生物学
- 発達生物学
- RNA 生物学
背景:
- miR-17∼92 マイクロRNA (miRNA) クラスタは,発育に不可欠であり,その失調は腫瘍形成に関連しています.
- 胚の発達において,miRNA発現の正確な制御が不可欠である.
研究 の 目的:
- 胚性幹細胞 (ESC) の分化過程におけるmiR-17∼92miRNAクラスタの動的調節を調査する.
- miR-17∼92クラスター内の個々のmiRNAの処理と発現を制御するメカニズムを解明する.
主な方法:
- ESC分化中のプライマリ miR-17∼92 (pri-miR-17∼92) トランスクリプト処理の分析
- miRNA 生成に関与する中間RNA構造と処理因子の特定
- miRNA生成におけるシス調節要素とタンパク質因子の役割 (CPSF3,ISY1) を調査する.
主要な成果:
- miR-17∼92クラスタの6つのmiRNAの相対的な発現は,ESCの微分化中に動的に調節される.
- Pri- miR-17∼92は,特定のpre- miRNAの生産を許可するために不可欠なプロジェニータ- miRNA (プロ- miRNA) の中間物質に処理されます.
- pri-miR-17∼92内の自己抑制性RNA構成はmiRNA処理を調節し,CPSF3とISY1はほとんどのクラスターmiRNAのプロ-miRNA生殖を媒介する.
結論:
- 発達的に調節されたプロミRNA処理は,miR-17∼92ミRNA発現の重要なコントロールポイントです.
- この研究は,開発中のmiR-17∼92クラスター発現を制御する新しい転写後の規制メカニズムを明らかにしています.
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