Transcript Diversification in the Nervous System: A to I RNA Editing in CNS Function and Disease Development

RNA editing by adenosine deaminases that act on RNA converts adenosines to inosines in coding and non-coding regions of mRNAs. Inosines are interpreted as guanosines and hence, this type of editing can change codons, alter splice patterns, or influence the fate of an RNA. A to I editing is most abundant in the central nervous system (CNS). Here, targets for this type of nucleotide modification frequently encode receptors and channels. In many cases, the editing-induced amino acid exchanges alter the properties of the receptors and channels. Consistently, changes in editing patterns are frequently found associated with diseases of the CNS. In this review we describe the mechanisms of RNA editing and focus on target mRNAs of editing that are functionally relevant to normal and aberrant CNS activity.

• Publication year

  2012

• Venue

  Frontiers in Neuroscience

• Publication date

  2012-07-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fnins.2012.00099PMID 22787438PMCID 3391646
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons.

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