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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...
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Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
RNA Editing02:23

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
MicroRNAs01:22

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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 ends...
MicroRNAs01:22

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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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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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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

La metiltransferasa de ARN humano BCDIN3D regula el procesamiento del microARN.

Blerta Xhemalce1, Samuel C Robson, Tony Kouzarides

  • 1Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

Cell
|October 16, 2012
PubMed
Resumen

Se encontró una nueva ARN metiltransferasa, BCDIN3D, en los precursores de O-metilato de microARN (miRNA), que inhibe su maduración. Este descubrimiento revela una nueva vía de metilación del miRNA que afecta el crecimiento de las células cancerosas.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • La bioquímica es la bioquímica.
  • Investigación de Investigación del Cáncer.

Sus antecedentes:

  • Los microARN (miRNA) son reguladores cruciales de los procesos biológicos, y su desregulación está relacionada con el cáncer.
  • La biogénesis de miRNA implica un procesamiento secuencial por Drosha y Dicer, generando los extremos de monofosfato 5' esenciales para la función.
  • El reconocimiento de Dicer del monofosfato 5' de los pre-miRNAs es crítico para una producción precisa de miRNA.

Objetivo del estudio:

  • Para identificar nuevos reguladores de la biogénesis del miRNA.
  • Para investigar el papel de las metiltransferasas de ARN en el procesamiento de miARN.
  • Para explorar la participación potencial de la regulación del miRNA en el cáncer.

Principales métodos:

  • Ensayos bioquímicos in vitro e in vivo para estudiar la actividad de BCDIN3D.
  • Análisis de los niveles de miRNA pre-miRNA y miRNA maduro después de la manipulación BCDIN3D.
  • Evaluación de los fenotipos de las células de cáncer de mama tras el agotamiento de BCDIN3D.

Principales resultados:

  • BCDIN3D, una ARN-metiltransferasa, fue identificada como un O-metilador del monofosfato 5' de los pre-miARN.
  • Se demostró que BCDIN3D fosfo-dimetila el pre-miR-145, reduciendo su procesamiento por Dicer.
  • El agotamiento de BCDIN3D en las células de cáncer de mama aumentó los niveles maduros de miR-145 y suprimió los fenotipos tumorigénicos.

Conclusiones:

  • BCDIN3D regula negativamente la maduración del miRNA a través de la O-metilación de los pre-miRNA.
  • Esta nueva vía de metilación de miRNA antagoniza el procesamiento dependiente de Dicer, impactando miR-145 y potencialmente otros miRNA.
  • Los hallazgos sugieren un nuevo mecanismo de regulación del miRNA relevante para la biología del cáncer.