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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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Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes
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Published on: July 28, 2017

RNA-binding protein AUF1 represses Dicer expression.

Kotb Abdelmohsen1, Kumiko Tominaga-Yamanaka, Subramanya Srikantan

  • 1Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA. abdelmohsenk@mail.nih.gov

Nucleic Acids Research
|October 16, 2012
PubMed
Summary

AUF1 (AU-binding factor 1) suppresses microRNA (miRNA) production by binding to DICER1 mRNA. This interaction reduces Dicer protein levels, thereby lowering mature miRNA synthesis.

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Area of Science:

  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNA (miRNA) biogenesis is crucial for cellular function and is tightly regulated.
  • Dicer is essential for processing precursor miRNAs into mature miRNAs.
  • Mechanisms regulating Dicer expression remain incompletely understood.

Purpose of the Study:

  • To investigate the role of RNA-binding protein AUF1 (AU-binding factor 1) in regulating Dicer expression.
  • To elucidate the interaction between AUF1 and DICER1 mRNA.

Main Methods:

  • Investigated the association of AUF1 with endogenous DICER1 mRNA.
  • Analyzed AUF1 interaction sites on DICER1 mRNA (coding region and 3'-UTR).
  • Assessed the impact of AUF1 modulation (silencing and overexpression) on DICER1 mRNA stability, Dicer levels, and miRNA synthesis.

Main Results:

  • AUF1 directly binds to DICER1 mRNA in both coding and 3'-UTR regions.
  • AUF1 binding decreases DICER1 mRNA stability and lowers Dicer protein levels.
  • Modulating AUF1 levels inversely affects Dicer expression and mature miRNA levels, without impacting pre-miRNA levels.

Conclusions:

  • AUF1 acts as a negative regulator of miRNA biogenesis.
  • AUF1 suppresses miRNA production by destabilizing DICER1 mRNA, leading to reduced Dicer levels.