The Molecular Symphony: IGF2BP1 and IGF2BP3 Choreography in Safeguarding IL-6 Against KSHV's Viral Host Shutoff

Presenter

Adriana Garber

Campus

UMass Amherst

Sponsor

Mandy Muller, Department of Microbiology, UMass Amherst

Schedule

Session 5, 3:30 PM - 4:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A32, Campus Center Auditorium, Row 2 (A21-A40) [Poster Location Map]

Abstract

Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) is an oncogenic gammaherpesvirus which has been implicated in the tumorigenesis of Kaposi’s Sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV has a biphasic lifecycle and exists in two forms in infected cells: a latent phase with minimal viral gene expression and a lytic phase with productive viral replication. During the lytic cycle, KSHV induces a large-scale mRNA degradation event in the cell, orchestrated by KSHV endoribonuclease SOX. While most cellular transcripts are highly downregulated during host shutoff via SOX, a subset of cellular mRNAs actively escape degradation. One of the most prominent cellular ‘escapees’ is cellular interleukin-6 (IL-6). We have found that IL-6 contains an element within its 3’ untranslated region (3’UTR) termed the SOX-resistance element (SRE), which confers protection from SOX-induced degradation. Previous studies identified that the m6A reader proteins IGF2BP1 and IGF2BP3 are strongly associated with the IL-6 SRE during lytic replication. To study the role of IGF2BP1 and IGF2BP3 on IL-6 SRE-mediated escape, we are adapting the MS2-MCP tethered assay system. This system consists of an ectopic mRNA cloned to MS2 stem loops, and a tagging Molecular Cap Protein (MCP) that binds to the MS2 stem loops, fused to a protein of interest along with a fluorescence protein. Using the MS2-MCP tethered assay, we will be able to force recruitment of IGF2BP1/3 to IL-6 and visualize its re-localization. By further understanding IGF2BP1/3 mediated stability of IL-6, we will be able to understand KSHV’s tumorigenesis and disease pathology. 

Keywords

Virology, RNA, Assay Development, Molecular Biology

Research Area

Cancer Studies

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