[R35] Discovery of Thermoregulatory RNAs
Ente: National Institute of General Medical Sciences
Scadenza: 2031-05-31
Importo max: 405.625 EUR
Paese: US
Descrizione
Abstract
Temperature variation is a critical environmental factor that influences microbial survival, pathogenesis, and
symbiosis, particularly during transitions from external environments into warm-blooded hosts. For pathogens
and members of the human gut microbiota, the ability to sense and adapt to host temperature fluctuations is
essential for survival. The study of thermoregulatory RNAs is an emerging field with great potential for discovery
and innovation. Thermoregulatory RNAs are structured elements that respond to heat stress, with most identified
examples known as RNA thermometers (RNATs) residing in the 5′ untranslated regions (UTRs) of mRNAs, where
they regulate translation. Despite their importance, the diversity of thermoregulatory RNAs, their natural
abundance, and the genes they regulate remain largely unexplored, and their potential roles in transcriptional
regulation are not yet understood.
Our central goals for the next five years are to expand the discovery and characterization of thermoregulatory
RNA elements in bacteria, phages, chloroplasts, and mitochondria, while also engineering synthetic RNATs with
improved regulatory properties. A major focus will be on bacterial pathogens, where RNATs regulate virulence
genes that drive infection and disease. By uncovering these elements, this work will reveal new RNA-based
targets for antibiotic development. In addition, we will identify novel RNAT classes, uncover transcriptional
thermoregulatory elements known as thermoterms, and test RNAT activity across prokaryotic and organelle
genomes to establish a broader framework for understanding how RNA structures mediate microbial and
organelle responses to heat stress. In parallel, synthetic RNATs will be developed as versatile genetic tools that
provide precise, modular, temperature-dependent control of gene expression.
These foundational advances are essential to achieve before broader ambitions can be realized, and they are
strategically designed to lay the groundwork for our long-term vision of building a comprehensive field of
thermoregulatory RNA biology that spans both fundamental discovery and applied innovation. This vision
includes exploring dual functional RNAs such as ribozymes and riboswitches that incorporate temperature
sensitivity into other regulatory mechanisms, extending RNAT discovery into eukaryotic nuclear genes and viral
RNAs, advancing RNA-targeted therapeutics, and applying RNATs in chloroplast engineering to enhance crop
resilience. Ultimately, this research will reveal how organisms use RNA to adapt to temperature stress, deepen
our understanding of gene regulation in response to heat stress, translate that knowledge into new strategies for
antibiotic development, and expand the toolkit of thermoregulatory RNAs for synthetic biology.
Istituzione: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
PI: Michael MICHAEL Abdelsayed
Progetto: 1R35GM165433-01
Settori: National Institute of General Medical Sciences
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