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PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA

Cellular & Molecular Immunology volume 18, pages 2334–2343 (2021)Cite this article

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Abstract

Cyclic GMP-AMP synthase (cGAS) is a key sensor critical for the recognition of DNA in the cytosol and catalyzes the synthesis of the second messenger cyclic GMP-AMP (cGAMP), which binds to the adapter protein MITA (also known as STING, MPYS, and ERIS) to initiate the innate immune response. How the binding of DNA to and the activation of cGAS are regulated remains poorly understood. Using a biochemical purification approach, we identified poly(rC)-binding protein 1 (PCBP1) as a cGAS-associated protein. PCBP1 was recruited to cGAS in a viral infection-dependent manner. PCBP1 directly bound to DNA and enhanced cGAS binding to its ligands, which was important for cGAS activation. Consistently, PCBP1 deficiency inhibited cytosolic DNA- and DNA virus-triggered transcription of downstream effector genes. These findings suggest that PCBP1 plays an important role in the cGAS-mediated innate immune response to DNA virus infection by promoting the binding of cGAS to viral DNA.

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Acknowledgements

We thank members of our laboratory for technical help and discussion. This work was supported by grants from the State Key R&D Program of China (2017YFA0505800 and 2016YFA0502102) and the National Natural Science Foundation of China (31830024, 31630045, and 31870870).

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Authors and Affiliations

  1. Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China

    Chen-Yang Liao, Cao-Qi Lei & Hong-Bing Shu

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  1. Chen-Yang Liao
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Contributions

H.-B.S., C.-Y.L., and C.-Q.L. designed the research; C.-Y.L. performed the research; H.-B.S., C.-Y.L., and C.-Q.L. analyzed the data; and H.-B.S., C.-Q.L., and C.-Y.L. wrote the paper.

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Correspondence to Hong-Bing Shu.

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Liao, CY., Lei, CQ. & Shu, HB. PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA. Cell Mol Immunol 18, 2334–2343 (2021). https://doi.org/10.1038/s41423-020-0462-3

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