{"doi":"10.1101/2021.07.02.450920","title":"Betacoronavirus-specific alternate splicing","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225523,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9008,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":71644,"name":"Bruce J. Aronow","orcid":"0000-0001-5109-6514","position":1,"is_corresponding":false},{"id":1841,"name":"Stephen B. Baylin","orcid":"0000-0003-3697-3798","position":2,"is_corresponding":false},{"id":231221,"name":"Daniel Butler","orcid":"0000-0002-3687-8419","position":3,"is_corresponding":false},{"id":227778,"name":"Jonathan Foox","orcid":"0000-0002-5705-3985","position":4,"is_corresponding":false},{"id":43059,"name":"Shawn Levy","orcid":"0000-0002-1369-5740","position":5,"is_corresponding":false},{"id":227777,"name":"Cem Meydan","orcid":"0000-0002-0663-6216","position":6,"is_corresponding":false},{"id":294641,"name":"Christopher Mozsary","orcid":"0000-0001-5116-4767","position":7,"is_corresponding":false},{"id":37867,"name":"Amanda Saravia-Butler","orcid":"0000-0001-7505-2743","position":8,"is_corresponding":false},{"id":44534,"name":"Deanne Taylor","orcid":"0000-0002-3302-4610","position":9,"is_corresponding":false},{"id":636891,"name":"Eve Syrkin Wurtele","orcid":"0000-0003-1552-9495","position":10,"is_corresponding":false},{"id":36370,"name":"Christopher E. Mason","orcid":"0000-0002-1850-1642","position":11,"is_corresponding":false},{"id":37850,"name":"Afshin Beheshti","orcid":"0000-0003-4643-531X","position":12,"is_corresponding":false},{"id":49925,"name":"Peter N. Robinson","orcid":"0000-0002-0736-9199","position":13,"is_corresponding":false},{"id":274601,"name":"Guy Karlebach","orcid":"0000-0002-1653-8206","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:26.581453Z","pmid":"34230929","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}