Lin28-let-7経路におけるDis3l2基板認識のメカニズム
Christopher R Faehnle1,2, Jack Walleshauser1,3,2, Leemor Joshua-Tor1,3,4,2
1W. M. Keck Structural Biology Laboratory 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Nature
|August 15, 2014
まとめ
Lin28-let-7経路は,Dis3l2がuridylated前駆体let-7を分解することを含む. 研究者は,Dis3l2を明らかにしました.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
背景:
- Lin28は,Let-7マイクロRNAのバイオゲネシスを阻害し,発育と癌に影響を及ぼします.
- Lin28は,UTT4/TUT7を,uridylate前駆体let-7 (pre-let-7) に勧誘する.
- Dis3l2はRNAのエクソソームホモログで,ウリジル化されたプレレット-7を分解する.
研究 の 目的:
- Dis3l2基板認識の分子メカニズムを解明する.
- Dis3l2 が,ウリジル化プレレット-7 をどのように結合し,分解するかを理解する.
主な方法:
- マウスDis3l2がオリゴURNAで複合したX線結晶図.
- RNA結合領域と触媒部位の構造分析.
主要な成果:
- オリゴURNAに結合するDis3l2の構造を決定した.
- 3つのRNA結合ドメインによって形成された開いたファネルを特定しました.
- オリゴU-テイドRNA認識のための広範なウラシル特異相互作用が明らかになりました.
結論:
- Dis3l2は,エクソソームの同位体とは異なるユニークな基板入り経路を使用しています.
- 3つのウラシル特異性ゾーンは,Dis3l2がウリジル化プレレット-7を認識し処理することを決定する.
- これは,Lin28-let-7の規制経路の最終段階を明確にします.
さらに関連する動画
関連する概念動画
MicroRNAs
20.9K
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...
20.9K
MicroRNAs
3.0K
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...
3.0K
Experimental RNAi
6.5K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.5K
RNA Interference
24.3K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
24.3K
piRNA - Piwi-interacting RNAs
6.0K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.0K
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K


