{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T17:05:12Z","timestamp":1768496712230,"version":"3.49.0"},"posted":{"date-parts":[[2021,7,2]]},"group-title":"Genomics","reference-count":74,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>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.<\/jats:p>","DOI":"10.1101\/2021.07.02.450920","type":"posted-content","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T19:36:06Z","timestamp":1625254566000},"source":"Crossref","is-referenced-by-count":0,"title":["Betacoronavirus-specific alternate splicing"],"prefix":"10.64898","author":[{"given":"Guy","family":"Karlebach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Aronow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen B.","family":"Baylin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Butler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Foox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cem","family":"Meydan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Mozsary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda M","family":"Saravia-Butler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanne M","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eve","family":"Wurtele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-1642","authenticated-orcid":false,"given":"Christopher E","family":"Mason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-531X","authenticated-orcid":false,"given":"Afshin","family":"Beheshti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-9199","authenticated-orcid":false,"given":"Peter N","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021070504551138000_2021.07.02.450920v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108427"},{"key":"2021070504551138000_2021.07.02.450920v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2011400"},{"key":"2021070504551138000_2021.07.02.450920v1.3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12839.e4"},{"key":"2021070504551138000_2021.07.02.450920v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.27"},{"key":"2021070504551138000_2021.07.02.450920v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature08909"},{"key":"2021070504551138000_2021.07.02.450920v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.11.018"},{"key":"2021070504551138000_2021.07.02.450920v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804947105"},{"key":"2021070504551138000_2021.07.02.450920v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.021"},{"key":"2021070504551138000_2021.07.02.450920v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005841"},{"key":"2021070504551138000_2021.07.02.450920v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040814"},{"key":"2021070504551138000_2021.07.02.450920v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.83"},{"key":"2021070504551138000_2021.07.02.450920v1.12","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1535607"},{"key":"2021070504551138000_2021.07.02.450920v1.13","doi-asserted-by":"crossref","unstructured":"Liang Zhang , Juan Wang , Raquel Mu\u00f1oz-Moreno , Min Kim , Ramanavelan Sakthivel , Wei Mo , Dandan Shao , Aparna Anantharaman , Adolfo Garc\u00eda-Sastre , Nicholas K. 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