RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner

Alys Peisley1, Bin Wu, Hui Yao

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Molecular Cell
|September 3, 2013
PubMed

Insights

Retinoic acid-inducible gene 1 (RIG-I) forms filaments on viral RNA, activating antiviral immunity. This filamentous assembly is key for RIG-I and MDA5 to detect viral dsRNA and signal interferon production.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are key sensors of viral RNA.
  • MDA5 filament formation upon dsRNA binding is known to be crucial for interferon signaling.
  • RIG-I's mechanism of dsRNA recognition and signaling activation remained less understood.

Purpose of the Study:

  • To elucidate the mechanism of RIG-I activation and filament formation upon viral dsRNA recognition.
  • To compare the signaling pathways activated by RIG-I and MDA5.
  • To define the role of filamentous architecture in innate antiviral immunity.

Main Methods:

  • Biochemical assays to study RIG-I binding to dsRNA in the presence and absence of ATP.
  • Filament formation assays for RIG-I and MAVS.
  • Interferon signaling activation assays.

Main Results:

  • RIG-I binds dsRNA as a monomer without ATP but forms filaments with ATP, propagating along the dsRNA.
  • RIG-I filaments directly induce MAVS filament formation without cofactors.
  • Proximity of RIG-I signaling domains within filaments is sufficient for interferon signaling.

Conclusions:

  • Filamentous assembly is a conserved mechanism for RIG-I and MDA5 in viral RNA detection.
  • RIG-I filament formation is essential for initiating interferon signaling.
  • This study highlights a versatile molecular platform for innate immune activation against viruses.

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