Unlocking the RNA Helicase Code: From Structural Insights to Therapeutic Strategies

RNA helicases play crucial roles in various cellular processes, and dysregulation of these enzymes is implicated in numerous diseases. Despite their potential as therapeutic targets, developing specific drugs for individual RNA helicases remains challenging due to shared binding sites and dynamic expression patterns. I aim to address these challenges by investigating the regulatory mechanisms of auxiliary RNA binding domains (RBDs) in RNA helicases and identifying novel modulators to regulate their activity. We recently elucidated the regulatory role of RBDs in the Drosophila RNA helicase MLE and propose similar regulatory mechanisms exist across other helicases which contain accessory RBDs. Through structural, biochemical, and cellular studies, I seek to understand how RBDs influence helicase function, identify RNA targets, and explore the impact of RBD-mediated regulation on protein interaction networks. Furthermore, we aim to discover small molecule modulators targeting dysregulated RNA helicases, potentially leading to novel therapeutic interventions. By addressing these aims, the research intends to advance our understanding of RNA helicase regulation and provide insights into potential therapeutic strategies for diseases associated with dysregulated helicases. Through interdisciplinary collaboration and innovative methodologies, we seeks to uncover fundamental principles governing RNA helicase regulation and their implications for human health.