Honors Theses

Date of Award

5-2025

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biomedical Sciences

Faculty Mentor

Glen M. Borchert

Advisor(s)

Jeffrey De Meis, Terrence J. Ravine, Raymond Langley

Abstract

Y RNAs are a poorly-studied class of small non-coding RNAs (sncRNAs) which have previously been implicated in the pathogenesis of different human diseases, including cardiac and autoimmune conditions, as well as certain cancers. In recent years, however, multiple studies have reported correlations between Y RNA expressions and disease outcomes in viral infections (e.g., influenza virus, HIV, HPV, and SARS-CoV-2) as well as potential mechanistic roles that Y RNAs may play in host anti-viral defense. These studies suggest that Y RNAs may be associated with upregulation of viral defense proteins as well as altered cell-cell communication during viral infections. To systematically evaluate the emerging role YRNAs play, we conducted a comprehensive literature review spanning 2000-2025, focusing on peer-reviewed studies that investigate Y RNA functions in viral infections. Our analysis revealed several key mechanistic insights: during influenza A virus infection, the ysRNA miR-1975 (derived from HY5) shows significant upregulation and gets packaged into exosomes where it enhances IFN-β production in neighboring cells. In HIV-1 infection, HY4 (RNY4) undergoes 5'-triphosphorylation due to viral suppression of DUSP11, enabling its binding to RIG-I and subsequent amplification of interferon responses. Perhaps most clinically relevant, plasma levels of HY4 demonstrate an inverse correlation with disease severity in COVID-19 patients, suggesting a protective function. These molecular findings are complemented by important clinical correlations, including the enrichment of Y RNA fragments in extracellular vesicles during viral infections (potentially serving as early biomarkers) and the association between HY1 expression and improved survival in HPV-positive head and neck cancers. The therapeutic potential of Y RNAs is further highlighted by several promising developments: synthetic Y RNA fragments have shown efficacy in blocking RSV entry by interfering with nucleolin binding, while the dysregulation of Y RNA profiles in severe COVID-19 cases provides important insights into viral immune evasion strategies. Despite these advances, significant knowledge gaps remain regarding the precise structural interactions between Y RNAs and immune sensors, as well as the need for standardized detection methods for clinical applications. Future research should prioritize high-resolution structural studies to elucidate Y RNA-immune sensor interactions, develop robust detection protocols for clinical settings, and validate therapeutic approaches in animal models. As our understanding of these versatile RNA molecules continues to grow, Y RNA research stands at the forefront of innovative approaches to combat viral infections, offering exciting possibilities for both diagnostic and therapeutic advancements that could significantly improve patient outcomes in infectious disease management.

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