archives@tulane.edu / A-to-I RNA editing, catalyzed by a family of enzymes called adenosine deaminases acting on RNA (ADARs), brings broad significance in various biological processes. To date, the roles of ADARs and its associated RNA editing in Epstein-Barr virus (EBV)’s life cycle and pathogenesis are still largely unknown. To fill this significant knowledge gap, we utilized our well-established next-generation RNA sequencing-based computational approaches and traditional molecular biology methodologies to elucidate the triangle relationship between ADARs, RNA-editing, and EBV infection. The expression of ADARs was first evaluated in a cohort of EBV-associated lymphoma cells. A constitutive expression of ADAR1, the predominant form of ADARs, was observed in the examined cells. In synchronous EBV reactivation cell models, we found that EBV reactivation led to a decreased expression of ADAR1 as well as a global suppression of A-to-I RNA editing. Further, we found that expression of the key viral trans-activator Zta inhibited ADAR1 expression in EBV-associated lymphoma cells. Analyses of the ADARs-mediated RNA editing events revealed novel editing sites on viral lytic transcripts. Knockdown of ADAR1 led to a global suppression of RNA-editing accompanied by a more robust EBV reactivation. Meanwhile, the enhanced expression of ADAR1 inhibited Zta’s expression and transactivation function. Together, our findings reveal a novel mechanism controlling the balance of EBV life cycle, in which ADAR1 and associated RNA editing events help maintain the viral latency by silencing Zta; whereas a bona fide lytic signal leads to high-level Zta expression by inhibiting ADAR1 and ADARs-mediated RNA editing. / 1 / Yi Yu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_121729 |
| Date | January 2020 |
| Contributors | Yu, Yi (author), Flemington, Erik (Thesis advisor), School of Science & Engineering Cell and Molecular Biology (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 121 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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