Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling

Peng Tan, Lian He, Jun Cui, Chen Qian, Xin Cao, Meng Lin, Qingyuan Zhu, Yinyin Li, Changsheng Xing, Xiao Yu, Helen Y. Wang, Rong Fu Wang

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP contributes to stabilization of the RIG-I-dsRNA interaction. Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity. Tan et al. identify a mitochondrial protein complex, WHIP-TRIM14-PPP6C, that positively regulates the antiviral RIG-I pathway. WHIP recognizes a ubiquitin message on RIG-I lysine 164 and regulates RIG-I mitochondrial membrane association. PPP6C dephosphorylates RIG-I in a positive feedback signal.

Original languageEnglish (US)
Pages (from-to)293-307.e5
JournalMolecular Cell
Issue number2
StatePublished - Oct 19 2017


  • ATPase domain
  • K63 ubiquitination
  • RIG-I-like receptor signaling
  • dephosphorylation
  • mitochondrial signalosome
  • ubiquitin binding

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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