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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

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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,...
Riboswitches01:56

Riboswitches

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.
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Regulation of Expression at Multiple Steps

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 addition of a...
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Transcriptional Regulation: Riboswitches

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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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Published on: March 3, 2015

Un mecanismo de vigilancia de ARNm que elimina las transcripciones que carecen de codones de terminación.

Pamela A Frischmeyer1, Ambro van Hoof, Kathryn O'Donnell

  • 1Institute for Genetic Medicine, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Science (New York, N.Y.)
|March 23, 2002
PubMed
Resumen

Los ARN mensajeros (ARNm) que carecen de codones de parada se degradan rápidamente por una vía dependiente de la traducción distinta de la desintegración del ARNm mediada por el disparate (NMD). Este mecanismo de descomposición ininterrumpido del ARNm se conserva en los mamíferos y regula la expresión génica.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Regulación de la expresión génica Regulación de la expresión génica
  • El metabolismo del ARN.

Sus antecedentes:

  • El control de calidad de la traducción es crucial para la salud celular.
  • La desintegración del ARNm mediada por el absurdo (NMD) degrada las transcripciones con codones de terminación prematura (PTC).
  • El destino de los ARNm que carecen de cualquier codón de terminación no estaba claro anteriormente.

Objetivo del estudio:

  • Para investigar el mecanismo de desintegración de los ARNm sin parar.
  • Para determinar si la desintegración del ARNm sin parar está relacionada con las vías conocidas de degradación del ARNm.
  • Para identificar las fuentes fisiológicas y la conservación de la descomposición ininterrumpida del ARNm.

Principales métodos:

  • Utilizó la levadura como organismo modelo.
  • Investigó las vías de descomposición del ARNm a través de enfoques genéticos y bioquímicos.
  • Examinado el decaimiento sin parar del ARNm en células de mamíferos.

Principales resultados:

  • Los ARNm que carecen de codones de terminación (ARNm sin parar) se degradan rápidamente en las levaduras.
  • La descomposición continua del ARNm requiere traducción, pero es mecánicamente distinta de la NMD y otras vías principales de descomposición.
  • Las transcripciones continuas se generan a partir de múltiples fuentes fisiológicas y su descomposición acelerada se conserva en las células de los mamíferos.

Conclusiones:

  • Una nueva vía de decaimiento del ARNm dependiente de la traducción, denominada decaimiento sin parar, se dirige a los ARNm que carecen de señales de terminación.
  • La descomposición continua se inicia cuando los ribosomas llegan al extremo 3' del ARNm.
  • Esta vía juega un papel importante en la regulación de la expresión de los ARNm que no terminan la traducción correctamente.