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Zika virus noncoding sfRNA sequesters viral restriction factors involved in RNA splicing and nucleic acid editing

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dc.contributor.authorOntiveros Valles, Jesús Gustavo, author
dc.contributor.authorWilusz, Jeffrey, advisor
dc.contributor.authorGeiss, Brian, committee member
dc.contributor.authorChen, Chaoping, committee member
dc.date.accessioned2019-06-14T17:06:44Z
dc.date.available2020-06-10T17:06:51Z
dc.date.issued2019
dc.description.abstractZIka virus (ZIKV) is a single-stranded positive sense RNA flavivirus that is transmitted primarily by Aedes aegypti. To date, all vector-borne flaviviruses are known to generate stable subgenomic flavivirus RNAs (sfRNA), due to the stalling of the major cytoplasmic 5'-3' exoribonuclease XRN1 at a knot-like three helix junction structure located in viral 3' untranslated regions (UTRs). Formation of sfRNAs not only stalls XRN1, but also represses its function. sfRNA decay intermediates accumulate to high levels in infected cells and studies with other flaviviruses have implicated sfRNAs in cytopathology. Our objective was to characterize the function of ZIKV sfRNAs to gain insight into ZIKV pathogenesis. Specifically, we identified host proteins that interact with ZIKV sfRNA and have begun to evaluate their role in cytopathology and pathogenesis. RNA pull-down experiments revealed that PHAX and SF3B1, critically important RNA splicing factors involved in nuclear-cytoplasmic shuttling, bind sfRNA. Additionally, the cytidine deaminase APOBEC3C was found to bind ZIKV sfRNA. Knockdown and subsequent overexpression of these RNA Binding Proteins (RBPs) identified the nucleic acid deaminase APOBEC3C and the splicing-associated factor PHAX as negative viral restriction factors whose activity may be suppressed and/or altered by sfRNA interaction during ZIKV infection. sfRNA interactions with the splicing factors also resulted in the accumulation of aberrantly spliced transcripts, possibly due to sequestration of the host cell proteins. Thus, in addition to targeting XRN1, sfRNAs appear to interact with a set of RBPs to disrupt cellular mRNA decay regulation as well as other RNA processing events in an effort to compromise multiple steps of RNA metabolism and promote pathogenesis.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierOntiverosValles_colostate_0053N_15433.pdf
dc.identifier.urihttps://hdl.handle.net/10217/195386
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectPHAX
dc.subjectSF3B1
dc.subjectZika
dc.subjectAPOBEC3C
dc.subjectXRN1
dc.subjectRNA
dc.titleZika virus noncoding sfRNA sequesters viral restriction factors involved in RNA splicing and nucleic acid editing
dc.typeText
dcterms.embargo.expires2020-06-10
dcterms.embargo.terms2020-06-10
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineCell and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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