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Mutations01:39

Mutations

Overview
Nuclear Export of mRNA02:31

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...
Nonsense-mediated mRNA Decay02:27

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,...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Nonsense-mediated mRNA Decay02:27

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,...

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Updated: Jul 8, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

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hERGのナンセンス変異は,人間の長QT症候群におけるナンセンス媒介のmRNA衰退によって変異mRNAトランスクリプトの減少を引き起こす.

Qiuming Gong1, Li Zhang, G Michael Vincent

  • 1Division of Cardiovascular Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.

Circulation
|June 20, 2007
PubMed
まとめ

無意味な媒介によるmRNAの衰退は,早死コドンを持つ長期QT症候群タイプ2 (LQT2) の患者でhERGmRNAのレベルを低下させる. 断片化されたタンパク質ではなく,この分解メカニズムが,LQT2.2におけるhERG mRNAの減少を説明している.

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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

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関連する実験動画

Last Updated: Jul 8, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
05:48

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

Published on: March 16, 2022

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

科学分野:

  • 分子生物学は分子生物学である.
  • 遺伝学 遺伝学とは
  • 心臓病学 心臓病学

背景:

  • ロングQT症候群2型 (LQT2) は,ヒトのエーテル・ア・ゴー・ゴー関連遺伝子 (hERG) の変異と関連しています.
  • LQT2変異の30%以上は,早期終結コドン (PTC) を生み出します.
  • 無意味な媒介によるmRNA崩壊 (NMD) は,PTCを含むmRNAを分解する既知の経路ですが,LQT2におけるその役割は未調査でした.

研究 の 目的:

  • LQT2.2におけるナンセンス媒介 mRNA 崩壊 (NMD) の役割を調査する.
  • PTCのLQT2患者で,NMDがhERG mRNAレベルに影響するかどうかを判断する.

主な方法:

  • 患者リンパ球におけるhERG mRNAのアレル特異的トランスクリプト定量化.
  • HEK293細胞と新生児ラット室内ミオサイトにおけるhERGミニゲンの分析.
  • サイクロヘキシミドとUpf1ノックダウンを用いたNMD阻害の評価.

主要な成果:

  • LQT2変異R1014XとW1001Xは,野生型と比較して,変異したhERGmRNAレベルが低下したことを示した.
  • PTCを搭載したhERGミニゲンは,mRNAレベルが低下したことを示した.
  • タンパク質合成の阻害またはUpf1が変異したhERG mRNAレベルを回復し,NMDの関与を確認しました.

結論:

  • LQT2のナンセンス変異は,切断されたタンパク質を生成することではなく,NMDを通じて変異したhERG mRNAレベルを低下させます.
  • hERG変異mRNAのNMD媒介の分解は,PTCまたはフレームシフト変異を有するLQT2患者の重要なメカニズムです.