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

Molecular cell 2017 Oct 19

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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. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

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. Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling. Molecular cell. 2017 Oct 19;68(2):293-307.e5