Chemical modifications to RNA molecules, which produce the so-called epitranscriptome, are prevalent in all forms of life. The functions of RNA modifications are yet unclear, although some modifications are thought to control the stability of the RNA. The goal of this project is to establish the patterns and functions of chemical modifications to protein-coding messenger RNAs (mRNAs) in the Archaea. This is especially important for Archaea, which thrive under extreme conditions - temperature, salinity, pressure, or pH - that are destabilizing for RNAs of most life forms. By studying mRNA modifications from Archaea in comparison to other organisms, this research is expected to establish Rules of mRNA Modification that will contribute to better understanding of the functional importance of this evolutionarily conserved process. The research results will be documented in a new web-based platform, called the mRNA Modification Database. This database will serve the broader RNA research community, STEM researchers, and the public. This research will be conducted by an interdisciplinary team involving researchers from academic, government, and industry labs, which will offer students the opportunity to engage in collaborative research across different professional settings.
This project seeks to expand understanding of the rules for establishment and function of the epitranscriptome in Archaea. A combination of unbiased techniques and genome-scale mapping methods will be used to identify, map, and compare the totality of ribonucleoside modifications present in a diverse range of extremophilic Archaea. Changes to the epitranscriptome due to environmental insults and specific genetic alterations will be determined. In parallel, experiments will be conducted to identify and characterize a suite of archaeal enzymes responsible for generating the archaeal epitranscriptome. A key aim is to establish the targeting sequences that result in site- and modification-specific alterations of select mRNAs. The rules of mRNA selection and targeting by each enzyme will be iteratively tested in vitro and then in vivo. Datasets, together with mapping techniques, mass spectrometry standards, and chemical and enzymatic characterizations of RNA modification enzymes, will be catalogued in a web-based mRNA Modification Database, which will be serve as a research and public resource.
This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences. Co-funding is provided by the Genetic Mechanisms Program, Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
