Tudor-SN媒介によるヒト細胞マイクロRNAの内核分解はG1/S相移行を促進する
Reyad A Elbarbary1,2, Keita Miyoshi1,2, Jason R Myers3
1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Science (New York, N.Y.)
|May 27, 2017
まとめ
Tudor- SN (TSN) エンドヌクレアスは,ヒト細胞内の機能性マイクロRNA (miRNA) を分解する. TSNを阻害すると,細胞サイクル進行が停止し,病的な細胞増殖を阻害する標的として TSNが示唆される.
科学分野:
- 分子生物学
- 遺伝子規制
- 生物化学
背景:
- マイクロRNA (miRNA) は遺伝子発現の重要なレギュレータである.
- 成熟したmiRNAの分解のメカニズムは,miRNAの生体生成よりも理解が少ない.
- Tudor-SN (TSN) は,miRNAの分解に潜在的役割を果たすエンドヌクレアースである.
研究 の 目的:
- 成熟したマイクロRNA (miRNA) の衰退におけるTudor-SN (TSN) の役割を調査する.
- TSNがmiRNAの分解を媒介するメカニズムを解明する.
- 細胞サイクル進行に対するTSN媒介のmiRNA分解の抑制の影響を評価する.
主な方法:
- 無タンパク質とアルゴナウト2負荷のmiRNAで再結合TSNを用いたin vitro分解測定法.
- TSN媒介による細胞崩壊の標的を特定するためのマイクロRNAシーケンシング.
- CRISPR-Cas9はTSNをノックアウトし,ヒト細胞での活動を抑制する.
主要な成果:
- TSNは,CAとUAのダイヌクレオチドの内核分解によるmiRNA分解を直接開始する.
- 分裂は,miRNAの末端から5つ以上のヌクレオチドの部位で好ましく起こります.
- CRISPR- Cas9 ノックアウトによるTSNの阻害は,miRNAのアップレギュレーションによるG1からSへのフェーズ移行時に細胞サイクル停止につながった.
結論:
- TSNはヒト細胞の機能的なmiRNAの分解を司る重要な内核酵素である.
- TSN媒介によるmiRNAの分解は,特定の分裂規則に従っている.
- TSN核酵素の活性を標的とした治療は,病的な細胞増殖を抑制する潜在的治療戦略です.
さらに関連する動画
08:33Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
Published on: December 5, 2017
15.0K
07:03Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
Published on: January 2, 2018
6.6K
関連する概念動画
01:23Negative Regulator Molecules
38.7K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.7K
02:34Inhibition of Cdk Activity
6.1K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
01:22MicroRNAs
4.2K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.2K
01:22MicroRNAs
24.4K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.4K
02:15Replicative Cell Senescence
4.5K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.5K
02:15M-Cdk Drives Transition Into Mitosis
6.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.7K