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Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...

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A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
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効率的なトランスクリプトーム幅のG4マッピングのための超特異的なG-四重体-コリスチン相互作用

Shijiong Wei1, Xiaobo Zhang1, Yilong Feng2

  • 1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Journal of the American Chemical Society
|March 6, 2025
PubMed
まとめ

抗生物質のコリスチン (COL) は,パラレルG四重複素 (G4s) に特異的に結合し,それらの結合を引き起こします. この発見により,ヒト細胞内のRNA G4sをマッピングする簡単な方法であるCoRP-seqの開発が可能になった.

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科学分野:

  • 化学生物学
  • ゲノミクス
  • 分子生物学

背景:

  • G四重複素 (G4s) は,ダイナミックなポリモルフィズムを持つ複雑な核酸構造であり,化学生物学の介入に課題をもたらす.
  • G4をターゲットにすることは 細胞のプロセスを理解し 新しい治療法を開発するのに 極めて重要です

研究 の 目的:

  • 小分子と特定のG4構造の相互作用を調査する.
  • ヒトのトランスクリプトームにおけるRNA G四重複体の有病率を評価するための新しい方法を開発する.

主な方法:

  • 抗生物質コリスチン (COL) と並列G四重複素 (G4s) の間の特定の相互作用を利用した.
  • COL誘発RNA G4の降水と配列決定 (CoRP-seq) プロトコルを開発し,G4の分離のために構造特異の集積と遠心分離を使用した.
  • CoRP-seqを適用して,ヒト細胞のトランスクリプトームにおけるRNA G4の流行を評価した.

主要な成果:

  • コリスチン (COL) は並列G四重複素 (G4s) に選択的に結合する.
  • この特殊な相互作用は,G4/COL複合体の結合を誘導し,遠心分離を可能にします.
  • CoRP-seqプロトコルは,超特異性,単純性,およびRNA G4のマッピングのための便利性を実証しました.

結論:

  • COLの特定のG4相互作用の発見は,G4ターゲティングのための新しいツールを提供します.
  • CoRP-seqは,RNA G-クアドルプレックスプロファイリングのシンプルで高度な方法を提供します.
  • この進歩は,G4マッピングとG4omicsのより広い分野における満たされていないニーズに対応します.