RETRACTED ARTICLE: Phosphor-IWS1-dependent U2AF2 splicing regulates trafficking of CAR-E-positive intronless gene mRNAs and sensitivity to viral infection
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Post-publication record
- Nature
- Retraction
- Reason
- Error in Data;Falsification/Fabrication of Data;Falsification/Fabrication of Results;Investigation by ORI;Misconduct - Official Investigation(s) and/or Finding(s);Misconduct by Author;Results Not Reproducible;Unreliable Results and/or Conclusions;
- Date
- 12/15/2021 0:00
- Flagged by OpenAlex?
- Yes
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Abstract
AKT-phosphorylated IWS1 promotes Histone H3K36 trimethylation and alternative RNA splicing of target genes, including the U2AF65 splicing factor-encoding U2AF2. The predominant U2AF2 transcript, upon IWS1 phosphorylation block, lacks the RS-domain-encoding exon 2, and encodes a protein which fails to bind Prp19. Here we show that although both U2AF65 isoforms bind intronless mRNAs containing cytoplasmic accumulation region elements (CAR-E), only the RS domain-containing U2AF65 recruits Prp19 and promotes their nuclear export. The loading of U2AF65 to CAR-Elements was RS domain-independent, but RNA PolII-dependent. Virus- or poly(I:C)-induced type I IFNs are encoded by genes targeted by the pathway. IWS1 phosphorylation-deficient cells therefore, express reduced levels of IFNα1/IFNβ1 proteins, and exhibit enhanced sensitivity to infection by multiple cytolytic viruses. Enhanced sensitivity of IWS1-deficient cells to Vesicular Stomatitis Virus and Reovirus resulted in enhanced apoptotic cell death via caspase activation. Inhibition of this pathway may therefore sensitize cancer cells to oncolytic viruses.
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The record
- Venue
- Communications Biology
- Topic
- RNA Research and Splicing
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Institute of Infection and Immunity
- Funders
- National Center for Advancing Translational SciencesNational Cancer InstituteNational Institutes of HealthPelotonia
- Keywords
- BiologyRNA splicingVesicular stomatitis virusSplicing factorExonRNACell biologyMolecular biologyAlternative splicingPhosphorylationRNA-binding proteinGeneVirologyVirusGenetics
- Has abstract in OpenAlex
- yes