RT Journal Article
SR Electronic
T1 Betacoronavirus-specific alternate splicing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.02.450920
DO 10.1101/2021.07.02.450920
A1 Guy Karlebach
A1 Bruce Aronow
A1 Stephen B. Baylin
A1 Daniel Butler
A1 Jonathan Foox
A1 Shawn Levy
A1 Cem Meydan
A1 Christopher Mozsary
A1 Amanda M Saravia-Butler
A1 Deanne M Taylor
A1 Eve Wurtele
A1 Christopher E Mason
A1 Afshin Beheshti
A1 Peter N Robinson
YR 2021
UL http://biorxiv.org/content/early/2021/07/02/2021.07.02.450920.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.