Transcriptome regulation by PARP13 in basal and antiviral states in human cells

Veronica F Busa; Yoshinari Ando; Stefan Aigner; Brian A Yee; Gene W Yeo; Anthony K L Leung

doi:10.1016/j.isci.2024.109251

Transcriptome regulation by PARP13 in basal and antiviral states in human cells

iScience. 2024 Feb 16;27(4):109251. doi: 10.1016/j.isci.2024.109251. eCollection 2024 Apr 19.

Authors

Veronica F Busa^{1

2}, Yoshinari Ando¹, Stefan Aigner^{3

4

5}, Brian A Yee^{3

4

5}, Gene W Yeo^{3

4

5}, Anthony K L Leung^{1

2

6

7}

Affiliations

¹ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
² McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
⁴ Stem Cell Program, University of California San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
⁵ Institute for Genomic Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
⁶ Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

The RNA-binding protein PARP13 is a primary factor in the innate antiviral response, which suppresses translation and drives decay of bound viral and host RNA. PARP13 interacts with many proteins encoded by interferon-stimulated genes (ISG) to activate antiviral pathways including co-translational addition of ISG15, or ISGylation. We performed enhanced crosslinking immunoprecipitation (eCLIP) and RNA-seq in human cells to investigate PARP13's role in transcriptome regulation for both basal and antiviral states. We find that the antiviral response shifts PARP13 target localization, but not its binding preferences, and that PARP13 supports the expression of ISGylation-related genes, including PARP13's cofactor, TRIM25. PARP13 associates with TRIM25 via RNA-protein interactions, and we elucidate a transcriptome-wide periodicity of PARP13 binding around TRIM25. Taken together, our study implicates PARP13 in creating and maintaining a cellular environment poised for an antiviral response through limiting PARP13 translation, regulating access to distinct mRNA pools, and elevating ISGylation machinery expression.

Keywords: Cell biology; Immune response; Molecular biology.

Abstract

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