Pcbp1 modulates the innate immune response by facilitating the binding of cgas to dna

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AN E1–E2 FUSION PROTEIN PRIMES ANTIVIRAL IMMUNE SIGNALLING IN BACTERIA

Article 08 February 2023 PCBP2 MAINTAINS ANTIVIRAL SIGNALING HOMEOSTASIS BY REGULATING CGAS ENZYMATIC ACTIVITY VIA ANTAGONIZING ITS CONDENSATION Article Open access 23 March 2022

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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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 Authors * Chen-Yang Liao View author publications You can also search for this author inPubMed Google Scholar * Cao-Qi Lei View author publications You can also search

for this author inPubMed Google Scholar * Hong-Bing Shu View author publications You can also search for this author inPubMed Google Scholar 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. CORRESPONDING AUTHOR Correspondence

to Hong-Bing Shu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

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 Download citation * Received: 05 January 2020 * Revised: 29 April 2020 * Accepted: 30 April 2020 * Published: 15 May 2020 * Issue Date: October 2021

* DOI: https://doi.org/10.1038/s41423-020-0462-3 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is

not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * cGAS * PCBP1 * DNA * virus * Innate Immunity