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Related Experiment Videos

Altered RNA editing in mice lacking ADAR2 autoregulation.

Yi Feng1, Christopher L Sansam, Minati Singh

  • 1Department of Pharmacology, Vanderbilt University School of Medicine, 465 21st Avenue South, 8160 Medical Research Building 3, Nashville, Tennessee 37232-8548, USA.

Molecular and Cellular Biology
|December 31, 2005
PubMed
Summary

ADAR2 RNA editing regulates its own protein levels. Ablating this autoediting in mice increases ADAR2 protein expression, showing it

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Area of Science:

  • Molecular Biology
  • RNA Editing
  • Gene Regulation

Background:

  • ADAR2 (adenosine deaminase acting on RNA 2) is an enzyme that edits mammalian RNAs, converting adenosine to inosine.
  • ADAR2 can edit its own pre-mRNA, creating a new splice site that leads to reduced functional protein expression.
  • This autoediting mechanism is hypothesized to be a negative autoregulatory strategy for ADAR2 protein levels.

Purpose of the Study:

  • To investigate whether ADAR2 RNA editing serves as a negative feedback mechanism to control ADAR2 protein expression.
  • To determine the in vivo role of ADAR2 autoediting in regulating ADAR2 protein levels and activity.

Main Methods:

  • Generation of genetically modified mice (homozygous deltaECS) lacking the ability to perform ADAR2 autoediting.

Related Experiment Videos

  • Comparison of ADAR2 protein expression and RNA editing activity in deltaECS mice versus wild-type mice across various tissues.
  • Main Results:

    • ADAR2 autoediting and subsequent alternative splicing were abolished in homozygous deltaECS mice.
    • ADAR2 protein expression was significantly increased in multiple tissues of deltaECS mice compared to wild-type controls.
    • Increased ADAR2 protein levels correlated with reduced autoediting and increased editing of other ADAR2 substrates.

    Conclusions:

    • ADAR2 autoediting is a critical regulatory mechanism controlling ADAR2 protein expression and enzymatic activity in vivo.
    • The findings support the model of ADAR2 RNA editing as a negative autoregulatory strategy to modulate enzyme levels.