Decoding RNA localization and local translation:… (R35GM159898) – Project Grant to University Of Florida

Abstract: RNA localization and local translation are vital for cellular function and adaptability. These processes confer several advantages, such as enabling proteins to be synthesized precisely when and where they are needed, reducing the reliance on protein transport, protecting rnas from degradation, and optimizing the cell's energy use. By coordinating RNA stability, transport, and translation within specific subcellular regions, local RNA regulation allows for rapid cellular responses to external cues. This is especially important in processes like homeostasis, differentiation, migration, immune responses, and synaptic plasticity. However, despite these advantages, several key aspects of RNA localization and local translation remain poorly understood. We lack a complete understanding of the molecular triggers, conditions, and mechanisms that determine where and when rnas are translated or how these processes mediate cellular adaptation. For instance, IT is unclear how cells prioritize which rnas to translate in response to specific stimuli or how different subcellular regions synchronize these responses. Local organelle regulation and the timing and regulation of localized translation, especially in relation to upstream open reading frames (uorfs) and RNA-binding proteins (rbps), also remain a mystery. These gaps in knowledge limit our understanding of how cells adapt to stress or adjust to physiological demands. The proposed research in this application aims to address these knowledge gaps using neurons as a model system. By leveraging advanced imaging tools and innovative turboid-mediated proximity labeling approaches, applied both in vivo and in vitro, this research will illuminate how local RNA regulation influences mitochondrial function under dynamic cellular demands. Additionally, IT will examine how the local molecular machinery shapes cellular responses and how these mechanisms are conserved or diverge across different species, shedding light on the evolutionary conservation of these processes. The emphasis will particularly be on identifying this regulation in response to adaptive stimuli. Comparing adaptive responses across different cell types and species will also offer crucial insights into how shared and divergent mechanisms determine cellular and organismal fitness and how disease susceptibility arises. This research application targets foundational questions in cellular biology and pathology, focusing on RNA-centric mechanisms that play critical roles in neuronal communication and influence the entire organism. By advancing our understanding of how subcellular RNA regulation and protein synthesis occur at neuronal junctions, this work aims to provide valuable insights relevant not only to neuroscience but to general medicine. The findings from this study could pave the way for new therapeutic approaches that extend beyond neurological disorders, addressing broader cellular and metabolic conditions. This interdisciplinary approach promises to push the boundaries of RNA biology, offering potential innovations that could benefit a wide range of medical fields.

Action	Obligated	Date
Amendment	$466,125	Jun 3, 2026
Original award	$466,125	Jul 25, 2025

Decoding RNA localization and local translation: key mechanisms of cellular adaption and function

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