eIF4E阻害タンパク質によるキャップ依存変換の調節

Joel D Richter¹, Nahum Sonenberg

¹Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. joel.richter@umassmed.edu

Nature

|February 4, 2005

まとめ

科学者たちは,メッセンジャーRNAキャップ構造を通して翻訳を調節するタンパク質ファミリーを発見しました. この発見は,細胞の成長,発達,そして癌のような病気を理解するために極めて重要です.

科学分野:

分子生物学は分子生物学である.
細胞生物学細胞生物学
遺伝学遺伝学とは

背景:

ユカリオットメッセンジャーRNA (mRNA) は5'キャップを持ち,これは翻訳開始に不可欠な変形グアノシンです.
翻訳開始因子eIF4Eは,タンパク質合成の重要なステップであるmRNAキャップに結合します.

研究の目的:

キャップ依存翻訳を調節する新しいタンパク質ファミリーを特定し,特徴づけること.
これらのタンパク質が翻訳開始に影響を与えるメカニズムを解明する.

主な方法:

この研究では,タンパク質発現と浄化,インビトロトランスレーションアッセイ,そしてモデル生物における潜在的遺伝子操作などの分子生物学技術が関与している可能性が高い.
生物情報分析は,新たに記述されたタンパク質ファミリー内の保存された配列を特定するために使用された可能性が高い.

主要な成果:

保存された配列モチーフを共有する新しいタンパク質ファミリーが特定されました.
このタンパク質ファミリーは,mRNAキャップ構造を含むメカニズムを通じて,キャップ依存翻訳を調節することが示されました.
特定されたタンパク質は,基本的な生物学的プロセスにおいて重要な役割を果たします.

結論:

このタンパク質ファミリーの発見は,翻訳レベルでの遺伝子発現の調節に関する新しい洞察を提供します.
この調節メカニズムは,成長,発達,腫瘍性変異を含む重要な細胞プロセスに関与しています.
これらのタンパク質に関するさらなる研究は,異変翻訳を含む疾患の治療標的を提供することがあります.

さらに関連する動画

10:40

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions

Published on: December 28, 2016

7.3K

08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

2.5K

関連する概念動画

02:07

Improving Translational Accuracy

11.6K

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...

11.6K

02:33

Initiation of Translation

24.7K

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...

24.7K

02:24

Regulation of Expression Occurs at Multiple Steps

20.2K

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

20.2K

01:52

Eukaryotic Transcription Inhibitors

9.1K

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...

9.1K

02:28

Leaky Scanning

4.5K

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

4.5K

01:23

Regulation of Expression at Multiple Steps

1.4K

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...