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Experimental RNAi02:15

Experimental RNAi

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...
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
MicroRNAs01:22

MicroRNAs

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...
MicroRNAs01:22

MicroRNAs

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 ends...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

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In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
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El silenciamiento de genes CUTs en ambos sentidos.

Nick Proudfoot1, Monika Gullerova

  • 1Sir William Dunn School of Pathology, South Parks Rd., OX1 3RE, University of Oxford, Oxford, UK. nicholas.proudfoot@path.ox.ac.uk

Cell
|November 21, 2007
PubMed
Resumen

Las transcripciones antisense en la levadura pueden desencadenar el silenciamiento de genes. La estabilización de estas transcripciones mediante el deterioro del exosoma conduce al reclutamiento de histona deacetilasa, lo que demuestra un nuevo mecanismo de regulación génica.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Genética La genética.
  • La epigenética es la epigenética.

Sus antecedentes:

  • Los genomas eucariotas se transcriben extensamente en varias moléculas de ARN, incluidas las transcripciones antisense y las transcripciones crípticas inestables (CUT).
  • El papel y la regulación de estas transcripciones no codificantes no se entienden completamente.

Objetivo del estudio:

  • Investigar el papel funcional de las transcripciones antisense en la regulación génica.
  • Determinar el mecanismo por el cual las transcripciones antisense podrían influir en la expresión génica.

Principales métodos:

  • Utilizando la levadura en ciernes (Saccharomyces cerevisiae) como un organismo modelo.
  • Empleando técnicas para deteriorar el complejo exosomal, lo que lleva a la estabilización de transcripciones de otra manera inestables.
  • Analizando el reclutamiento de las histonas desacetilasas (HDAC) en respuesta a las transcripciones antisense estabilizadas.

Principales resultados:

  • Se demostró que las transcripciones antisense estabilizadas pueden mediar el silenciamiento de genes en la levadura.
  • Se demostró que este silenciamiento genético se produce a través del reclutamiento de histonas desacetilasas para apuntar a los loci genéticos.
  • Proporcionó evidencia de que el deterioro del exosoma es clave para estabilizar las transcripciones antisense para las funciones reguladoras.

Conclusiones:

  • Las transcripciones antisense, cuando se estabilizan, pueden actuar como potentes mediadores del silenciamiento de genes.
  • El reclutamiento de la histona desacetilasa es un componente crítico de la vía de silenciamiento de genes mediada por antisenso.
  • Este estudio revela una nueva capa de regulación génica que involucra ARN no codificante y modificaciones epigenéticas.