Characterizing the Role of Human Antigen R (HuR) in Protecting IL-6 mRNA from Viral Degradation

Presenter

Shai Vilner Shimoni

Campus

UMass Amherst

Sponsor

Mandy Muller, Department of Microbiology, UMass Amherst

Schedule

Session 4, 2:30 PM - 3:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board C15, Poster Showcase Room (163), Row 2 (C11-C20) [Poster Location Map]

Abstract

Kaposi Sarcoma-Associated herpesvirus (KSHV) is a herpesvirus responsible for the development of several malignancies. KSHV persists in its host for decades and is, therefore, almost continuously in need of hijacking resources from its host. To co-opt these resources, KSHV uses a unique strategy: widespread RNA decay. This massive viral-induced degradation leads to the loss of more than 70% of host cellular mRNAs, freeing all the necessary resources for viral expression. Although most of the host transcriptome is affected by KSHV, some transcripts escape degradation. We have previously identified a ~200nt RNA element located at the 3’UTR of the escaping transcripts. This RNA element has been shown to work in concert with RNA-binding proteins (RBPs) to form a protective complex. One such RBP is HuR (also known as ELAV1), an RNA-binding protein known to affect the stability of its mRNA target. To further elucidate the protective mechanisms triggered by HuR, we are characterizing its role during KSHV infection through knockdown and complementation assays. Additionally, we designed HuR truncation mutants lacking specific RNA recognition motifs (RRMs), to identify the domains responsible for the interaction between HuR and the transcripts spared from viral-induced degradation. By analyzing the mechanisms that allow certain mRNAs to escape degradation, our research aims to provide insights into the intricate regulation of mRNA stability and fate during KSHV infection. The role of RNA-binding proteins in mRNA stability has implications for our understanding of host-viral interactions and may inform the development of targeted therapeutics against KSHV and related viral infections.

Keywords

virus, RNA decay, RNA stability, RNA-protein interactions, oncogenic virus

Research Area

Genetics

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