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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...
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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...
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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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RNA Interference01:23

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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.
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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
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La supresión del tumor mediante la vigilancia del ARN

Robert P Fisher1

  • 1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Science (New York, N.Y.)
|April 20, 2023
PubMed
Resumen

Una quinasa dependiente de ciclina recién descubierta apunta y degrada las moléculas de ARN que terminan la transcripción prematuramente. Este mecanismo asegura la expresión genética adecuada mediante la eliminación de transcripciones de ARN defectuosas.

Área de la Ciencia:

  • Biología molecular
  • La bioquímica
  • La genética

Sus antecedentes:

  • La transcripción produce moléculas de ARN a partir de plantillas de ADN.
  • La terminación prematura de la síntesis de ARN puede conducir a transcripciones aberrantes.
  • Los mecanismos celulares existen para manejar y degradar el ARN no funcional.

Objetivo del estudio:

  • Identificar el mecanismo molecular responsable de la degradación de los ARN terminados prematuramente.
  • Aclarar el papel de las cinasas dependientes de la ciclina en el control de la calidad del ARN.

Principales métodos:

  • Se utilizaron modelos de levadura para la detección genética.
  • Se emplean ensayos bioquímicos para controlar la degradación del ARN.
  • Se realizó una espectrometría de masas para identificar las proteínas que interactúan.

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Principales resultados:

  • Se identificó una cinasa dependiente de ciclina (CDK) específica que se une al ARN terminado prematuramente.
  • Se demostró que la actividad de CDK es esencial para la degradación de estas transcripciones aberrantes.
  • Descubrió una nueva vía que vincula la actividad de CDK a la vigilancia del ARN.

Conclusiones:

  • Las cinasas dependientes de la ciclina juegan un papel crítico en el procesamiento del ARN y el control de calidad.
  • La degradación dirigida de ARN terminados prematuramente por las CDK es un proceso celular conservado.
  • Este hallazgo proporciona nuevos conocimientos sobre la regulación de la expresión génica y las vías de vigilancia del ARN.