RIG1/MDA5

• Activation of RIG-1

  Occurs upon binding of dsRNA
• RIG-1

  • Large, multidomain protein aka Retinoic Acid Inducible Gene 1
  • Functions as a pattern recognition receptor (PRR)
  • Member of double-stranded RNA (dsRNA)
  • First line of defense against various viral families
  • Implicated in responding to intracellular bacterial infections
• RIG-1 activation

  1. DsRNA binding domains and ATPase core are activated upon binding of dsRNA

  2. Controls the cell and found in the cytoplasm, nucleus, mitochondria

  3. Patrols cells, samples RNAs, binds to them, and releases them while searching for viral RNA targets

  4. Developed strategies to be stimulated upon binding with viral RNAs

  5. Encountering viral RNA molecules upon infection results in the formation of a stable, single-active conformation

  6. Pathogen RNAs trigger conformational changes anchoring the RNA inside the RIG-1 receptor and triggering the release of CARDS

  7. Selective activation by dsRNA, not DNA

  8. Blunt RNA duplexes trigger rapid signalling response and potent IFN induction

  9. Requires specific interactions with the 5' terminus of the RNA duplex (RIG-1 binds to 5'ppp-dsRNA)