Betacoronavirus-specific alternate splicing

Karlebach, G.; Aronow, B. J.; Baylin, S. J.; Butler, D.; Foox, J.; Levy, S.; Meydan, C.; Mozsary, C.; Saravia-Butler, A. M.; Taylor, D. M.; Wurtele, E.; Mason, C.; Beheshti, A.; Robinson, P. N.

doi:10.1101/2021.07.02.450920

bioRxiv · 10.1101/2021.07.02.450920

Betacoronavirus-specific alternate splicing

Karlebach, G.·Aronow, B. J.·Baylin, S. J.·Butler, D.·Foox, J.·Levy, S.·Meydan, C.·Mozsary, C.·Saravia-Butler, A. M.·Taylor, D. M.·Wurtele, E.·Mason, C.·Beheshti, A.·Robinson, P. N.

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Abstract

Viruses can subvert a number of cellular processes in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection as well as datasets from the betacoronaviruses SARS-CoV and MERS as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification and a smaller number of exons than differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by DAS and DGE in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS, potentially modifying a broad range of cellular functions and affecting a diverse set of genes and biological functions.

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Karlebach, G., Aronow, B. J., Baylin, S. J., Butler, D., Foox, J., Levy, S., Meydan, C., Mozsary, C., Saravia-Butler, A. M., Taylor, D. M., Wurtele, E., Mason, C., Beheshti, A., Robinson, P. N.. 2021-07-02. Betacoronavirus-specific alternate splicing. https://doi.org/10.1101/2021.07.02.450920

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