Jove
Visualize
Contáctanos
JoVE
x logofacebook logolinkedin logoyoutube logo
ACERCA DE JoVE
Visión GeneralLiderazgoBlogCentro de Ayuda JoVE
AUTORES
Proceso de PublicaciónConsejo EditorialAlcance y PolíticasRevisión por ParesPreguntas FrecuentesEnviar
BIBLIOTECARIOS
TestimoniosSuscripcionesAccesoRecursosConsejo Asesor de BibliotecasPreguntas Frecuentes
INVESTIGACIÓN
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchivo
EDUCACIÓN
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualCentro de Recursos para ProfesoresSitio de Profesores
Términos y Condiciones de Uso
Política de Privacidad
Políticas

Videos de Conceptos Relacionados

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,...

También podría leer

Artículos Relacionados

Artículos vinculados a este trabajo por autores compartidos, revista y gráfico de citas.

Ordenar por
Same author

Target Trial Emulation of Vaccine Effectiveness in 5- to 17-years-olds with Prior SARS-CoV-2 Infection.

Nature communications·2026
Same author

Pilot proteomics study for identifying a pollution exposure signature in firefighters.

Journal of exposure science & environmental epidemiology·2026
Same author

Risk of venous thromboembolism associated with short-term exposure to fine particulate matter (PM<sub>2.5</sub>) and ozone air pollution.

Research and practice in thrombosis and haemostasis·2025
Same author

Age-Related Changes in the Clinical Picture of Long COVID.

Journal of the American Geriatrics Society·2025
Same author

A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.

Frontiers in systems biology·2025
Same author

Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.

Scientific reports·2025

Video Experimental Relacionado

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

Las mutaciones sin sentido en el hERG causan una disminución en las transcripciones de ARNm mutantes por la

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
Resumen

La desintegración del ARNm mediada por el absurdo reduce los niveles de ARNm hERG en pacientes con síndrome de QT largo tipo 2 (LQT2) con codones de terminación prematura. Este mecanismo de degradación, no las proteínas truncadas, explica la reducción del ARNm hERG en LQT2.

Más Videos Relacionados

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

Videos de Experimentos Relacionados

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

Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Genética La genética.
  • Cardiología Cardiología.

Sus antecedentes:

  • El síndrome de QT largo tipo 2 (LQT2) está relacionado con mutaciones en el gen humano relacionado con el ether-a-go-go (hERG).
  • Más del 30% de las mutaciones LQT2 crean codones de terminación prematura (PTC).
  • La desintegración del ARNm mediada por el absurdo (NMD) es una vía conocida para degradar el ARNm que contiene PTC, pero su papel en LQT2 no se exploró.

Objetivo del estudio:

  • Para investigar el papel de la desintegración del ARNm mediada por el no sentido (NMD, por sus siglas en inglés) en LQT2.2.
  • Para determinar si la NMD afecta los niveles de ARNm hERG en pacientes LQT2 con PTC.

Principales métodos:

  • Cuantificación del transcrito específico del alelo del ARNm hERG en linfocitos de pacientes.
  • Análisis de los minigenes hERG en las células HEK293 y los miocitos ventriculares neonatales de ratas.
  • Evaluación de la inhibición de la NMD utilizando cicloheximida y knockdown de Upf1.

Principales resultados:

  • Las mutaciones LQT2 R1014X y W1001X mostraron niveles reducidos de ARNm hERG mutante en comparación con el tipo silvestre.
  • Los minígenos hERG portadores de PTCs exhibieron niveles disminuidos de ARNm.
  • La inhibición de la síntesis de proteínas o Upf1 restauró los niveles mutantes de ARNm hERG, lo que confirma la participación de la DMN.

Conclusiones:

  • Las mutaciones sin sentido de LQT2 disminuyen los niveles mutantes de ARNm hERG a través de NMD, no produciendo proteínas truncadas.
  • La degradación mediada por NMD del ARNm mutante hERG es un mecanismo significativo en pacientes LQT2 con PTC o mutaciones de cambio de marco.