PCBP2 Maintains Antiviral Signaling Homeostasis by Regulating CGAS Enzymatic Activity Via Antagonizing Its Condensation

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Mar 24

PMID 35322803

Authors

Haiyan Gu

Jing Yang

Jiayu Zhang

Ying Song

Yao Zhang

Pengfei Xu

Yuanxiang Zhu

Liangliang Wang

Pengfei Zhang

Lin Li

Dahua Chen

Qinmiao Sun

Affiliations

Soon will be listed here.

Abstract

Cyclic GMP-AMP synthase (cGAS) plays a major role in detecting pathogenic DNA. It produces cyclic dinucleotide cGAMP, which subsequently binds to the adaptor protein STING and further triggers antiviral innate immune responses. However, the molecular mechanisms regulating cGAS enzyme activity remain largely unknown. Here, we characterize the cGAS-interacting protein Poly(rC)-binding protein 2 (PCBP2), which plays an important role in controlling cGAS enzyme activity, thereby mediating appropriate cGAS-STING signaling transduction. We find that PCBP2 overexpression reduces cGAS-STING antiviral signaling, whereas loss of PCBP2 significantly increases cGAS activity. Mechanistically, we show that PCBP2 negatively regulates anti-DNA viral signaling by specifically interacting with cGAS but not other components. Moreover, PCBP2 decreases cGAS enzyme activity by antagonizing cGAS condensation, thus ensuring the appropriate production of cGAMP and balancing cGAS-STING signal transduction. Collectively, our findings provide insight into how the cGAS-mediated antiviral signaling is regulated.

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