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Nuclear Export of mRNA
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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...
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Nonsense-mediated mRNA Decay
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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,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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mRNA Stability and Gene Expression
5.5K
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
Cis-acting Elements involved in mRNA stability
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Chromatin Structure Regulates pre-mRNA Processing
6.9K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
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Regulated mRNA Transport
6.2K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.2K
Regulation of Expression Occurs at Multiple Steps
22.2K
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...
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...
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高通量でmRNAの分解を制御する乱れた領域の解読
Joseph H Lobel1, Nicholas T Ingolia2,3
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Nature
|April 24, 2025
まとめ
本質的に乱れたタンパク質領域は,mRNAの安定性と翻訳に影響を与えることで遺伝子発現を制御する. アロマティック残留パターンは,この調節を促す重要な分子特性であり,しばしばmRNA崩壊経路と相互作用する.
科学分野:
- 分子生物学
- 生物化学
- 遺伝学
背景:
- タンパク質の内在的に乱れた領域 (IDR) は,固定された構造なしに重要な機能を果たします.
- IDRsがメッセンジャーRNA (mRNA) の安定性と翻訳を調節するメカニズムは十分に理解されていません.
研究 の 目的:
- 本質的に無秩序なタンパク質領域が遺伝子発現を制御する分子特性と経路を特定する.
- これらの領域がmRNAの安定性と翻訳にどのように影響するか解明する.
主な方法:
- 何百もの規制の不規則な要素の高通量機能プロファイリング
- 主要な分子特性を特定するための系統的変異と機械学習分析.
- mRNA分解機構との相互作用を調査する生化学的測定法.
主要な成果:
- 分子特性の複雑なパターン,特に芳香質残留物の存在と配置は,IDRの規制活動を強く予測する.
- 似たような芳香的残留パターンを持つ様々なタンパク質の配列は,mRNAの安定性と翻訳に類似した効果を示している.
- 多くのIDRは,mRNAの崩壊機構のコアコンポーネントと相互作用することで,その調節機能を果たします.
結論:
- この研究では,固有のタンパク質領域による遺伝子発現の調節に責任を負う特定の分子特性と生化学経路が定義されています.
- 発見は,細胞プロセスにおける構造化されていないタンパク質の機能を支配するより広範な原理の洞察を提供します.


