酵母エクソソームは,マクロ分子ケージとして機能し,RNA基板を分解のためにチャネル化する

Fabien Bonneau¹, Jérôme Basquin, Judith Ebert

¹Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.

Cell

|November 3, 2009

まとめ

エクソソーム複合体は,Rrp44核酵素を用いてRNAを分解する. RNAはエクソソームの核を通ってRrp44核酵素部位に到達し,分解します.

科学分野:

分子生物学は分子生物学である.
構造生物学構造生物学とは
バイオケミストリーバイオケミストリー

背景:

エクソソームは,RNAの分解に不可欠なマクロ分子複合体である.
ユーカリオットのエクソソーム・コアは,プロカリオットの複合体と構造を共有しているが,触媒的に惰性である.
Rrp44核酵素は,10つのサブユニットからなるユーカリオットエクソソームの活性化に不可欠である.

研究の目的:

活性10サブユニットエクソソーム内のRrp44核酵素の機能を調査する.
Rrp44がエクソソームの核と相互作用する構造的基礎を解明する.
ユカリオットのエクソソームによるRNA分解のメカニズムを理解する.

主な方法:

酵母Rrp44-Rrp41-Rrp45複合体のX線結晶学 (3.0A解像度) について.
RNA結合と分解経路を分析するための生化学研究.

主要な成果:

結晶構造は,Rrp44がエクソソームの核と相互作用し,その核酶部位のアクセシビリティを明らかにしています.
生物化学的データによると,RNAはエクソソームコアの中央チャネルを通ってRrp44エクソリボニュクレアース部位に到達する.
保存されたチャネリングメカニズムは,3'拡張を持つRNA複合体の過程的な分解を容易にし,ヘリコゼとは独立しています.

結論:

ユーカリオットのエクソソームは,保存されたRNAスレッドメカニズムを分解のために利用します.
エクソソームの核は触媒的活動を失い,基板の採用と結合はプロカリオートから保存されます.
Rrp44核酵素の活動は,機能的なエウカリオスのエクソソームの鍵であり,ユニークなチャネリング経路を使用します.

さらに関連する動画

09:15

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC

Published on: May 9, 2020

09:59

Preparation of Exosomes for siRNA Delivery to Cancer Cells

Published on: December 5, 2018

関連する概念動画

02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability

02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...

02:31

Nuclear Export of mRNA

01:36

Overview of Exosomes

Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...

01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...

02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...

関連する実験動画