Brown BIOL1220:Notebook/SynBio in Theory and Practice/Genes/ADAR

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Adenosine Deaminases that act on RNA (ADARs)

The Functions of the ADAR Family

  • Three members of this deaminase family are known: ADAR 1, ADAR 2, and ADAR 3 that share a common modular domain structure.
3D structure of conserved ADAR regions
3D structure of conserved ADAR regions
  • ADARs modify pre-mRNA and recognize structural determinants in the RNA.
  • In mice, the editosomes with ADAR proteins require some cis-acting elements like an intronic 'editing-site complementary sequence (ECS)'. Although evolutionarily conserved, the actual role of ECS is not yet elucidated in humans. A representation of the editing complex is shown below.

Image:ADAR_editosome.png

  • The deamination of adenosines (A) to inosine (I) is the most common editing event.

Why edit pre-mRNA?

  • To increase genetic diversity through changes in the transcriptome. For an example of this, see below.

ADAR Functions in Receptors

  • Deamination by editing in pre-mRNAs encodes a variety of subunits of ionotropic glutamate receptors (GluRs).
  • Editing at the Q/R site of the GluR2 (GluRB) subunit of AMPA receptors changes a Gln codon CAG to an Arg codon CIG, which makes the heteromeric receptor impermeable to Ca2+ ions.
  • Editing of 5-HT2C subtype serotonin receptor mRNA results in receptor isoforms with reduced G-protein coupling efficiency (reviewed by Gerber and Keller, 2001).

References

  1. Blanc, V, Davidson, NO. C-to-U RNA editing: mechanisms leading to genetic diversity. 2003 J Biol Chem
  2. Bass, BL. RNA editing by adenosine deaminases that act on RNA. 2002 Annu Rev Biochem
  3. Melcher, T, Maas, S, Herb, A, Sprengel, R, Higuchi, M, Seeburg, PH. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. 1997 J Biol Chem
  4. Gerber, AP, Keller, W. RNA editing by base deamination: more enzymes, more targets, new mysteries. 2001 Trends Biochem Sci
  5. Polson, AG, Crain, PF, Pomerantz, SC, McCloskey, JA, Bass, BL. The mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysis. 1992 Biochemistry
  6. http://www.reactome.org/cgi-bin/eventbrowser
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