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Related Concept Videos

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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...
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

Hui-Wen Chen1,2, Chung-Pei Ma1, En Chin1,2

  • 1Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

International Journal of Molecular Sciences
|June 19, 2024
PubMed
Summary

A-to-I RNA editing in the Unc80 gene, dependent on ADAR2, impacts brain neuronal activity and olfactory perception. This study reveals how Unc80 editing variations affect glutamate levels and odor detection behaviors in mice.

Keywords:
RNA editingUnc80neuronal activityolfactory perception

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • A-to-I RNA editing, mediated by ADAR proteins, diversifies RNA signatures for physiological needs.
  • The functions of many RNA editing sites remain uncharacterized.
  • The Unc80 gene exhibits brain-specific expression and conserved codon-altering editing events, yet its functions are largely undefined.

Purpose of the Study:

  • To investigate the neurophysiological functions of Unc80 and the impact of its RNA editing.
  • To determine the ADAR dependency and tissue specificity of Unc80 editing.
  • To elucidate the role of Unc80 editing in olfactory sensory perception and neuronal activity.

Main Methods:

  • Utilized CRISPR/Cas9 to generate Unc80 knock-in mouse models with natural editing variations (gain-of-editing and loss-of-editing).
  • Measured basal neuronal activity in olfactory regions and glutamate levels in olfactory bulbs.
  • Conducted behavioral analyses for odor detection and dishabituation responses.
  • Performed transcriptomic analysis of the olfactory bulb.

Main Results:

  • Unc80 editing is ADAR2-dependent and brain-exclusive.
  • Gain-of-editing Unc80 variants (Unc80G/G) showed heightened basal neuronal activity and increased glutamate in olfactory regions.
  • Mice with Unc80 deficiency or loss-of-editing exhibited prolonged odor exploration and heightened dishabituation.
  • Transcriptomic analysis revealed significant gene expression alterations in the olfactory bulb, correlating with physiological and behavioral findings.

Conclusions:

  • Unc80 editing significantly influences neurophysiological functions within the olfactory system.
  • ADAR2-mediated Unc80 editing impacts neuronal activity, neurotransmitter dynamics, and olfactory perception.
  • This research provides insights into the molecular mechanisms underlying olfactory processing and neuronal activity regulation.