ヒト核RNAエクソソーム-MTR4複合体の冷凍-EM構造によって照らされたヘリカーゼ依存RNA分解

Eva-Maria Weick¹, M Rhyan Puno², Kurt Januszyk¹

¹Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Cell

|June 16, 2018

まとめ

Mtr4ヘリケーゼはRNAの構造を解き放ち,RNAエクソソーム複合体の分解を容易にする. この相互作用は,Mtr4がRNAとエクソソームにどのように関わり,分解を誘導するかを明らかにします.

科学分野:

分子生物学
構造生物学
生物化学

背景:

RNAエクソソームは RNAの分解に不可欠な複合体です
Mtr4のようなRNAヘリコースは,エクソソームと相互作用することが知られている.
RNAの結合と分解の仕組みを理解することは不可欠です.

研究の目的:

Mtr4ヘリコースがRNAエクソソームと相互作用するメカニズムを解明する.
Mtr4が構造化されたRNA基板を分解する仕組みを理解する.
Mtr4エクソソームの相互作用の構造的基礎を決定する.

主な方法:

多種からの14サブユニットMtr4を含むRNAエクソソムの再構成.
凍結電子顕微鏡 (cryo-EM) で,MTR4が停止したヒトエクソソムの構造を決定する.
基質の解き放たれと分解を評価する生化学的測定法

主要な成果:

Mtr4ヘリケーゼは構造化されたRNA基板を解き放ち,エクソソームによる分解を促進する.
Cryo-EM構造は,Mtr4がエクソソームの核の上に位置し,中央チャネルとDIS3の活性部位にRNAがあることを示しています.
MPP6はMtr4をエクソソームに結合し,EXOSC10の触媒モジュールはRNAが関与するMtr4によって置き換えられる.
エクソソームの核への競争は RNAを分解させるメカニズムを示唆しています

結論:

Mtr4は,RNAエクソソームによる分解のための構造化されたRNAをターゲットにする上で重要な役割を果たします.
決定された構造は,Mtr4エクソソームの相互作用とRNA処理に関する原子レベルの洞察を提供します.
このメカニズムは,エクソソーム複合体による効率的かつ特定のRNA分解を保証します.

キーワード:

RNAの分解 RNA-タンパク質複合体 SF2 についてエクソリボニュクレアスエクソソームヘリコースハイドロラーゼ原子力リボヌクレアーストランスロカゼ

さらに関連する動画

05:05

Preparation of High-Temperature Sample Grids for Cryo-EM

Published on: July 26, 2021

4.3K

09:26

Identification of Footprints of RNA:Protein Complexes via RNA Immunoprecipitation in Tandem Followed by Sequencing RIPiT-Seq

Published on: July 10, 2019

11.2K

関連する概念動画

01:23

RNA Structure

79.2K

Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...

79.2K

01:19

RNA Structure

7.7K

The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...

7.7K

01:32

RNA Splicing

60.7K

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

60.7K

00:58

Eukaryotic RNA Polymerases

27.2K

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...

27.2K

01:53

RNA Stability

35.8K

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

35.8K

02:31

Nuclear Export of mRNA

8.8K

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...