An international team led by researchers from Baylor College of Medicine with the National Institutes of Health Extracellular RNA Communication Consortium and the Bogdan Mateescu lab at ETH Zürich and the University of Zürich has developed a powerful new resource for studying RNA. extracellular (exRNA), a new form of cell-to-cell communication. The study, published in the journal cell genomicslays the foundation for examining how exRNA and its carrier proteins found in body fluids function in a healthy and diseased environment, potentially providing a means to accurately implement early detection and monitor disease processes.
“Ribonucleic acid or RNA is a type of genetic material that is present within all living cells. It is known to act primarily as a messenger carrying DNA-encoded instructions for protein synthesis,” said corresponding co-author Dr. Dr. Aleksandar. Milosavljevic, Professor and the Henry and Emma Meyer Chair of Molecular Genetics at Baylor. He is also the director of the Graduate Program in Quantitative and Computational Biosciences and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. The Milosavljevic Lab is host to the exRNA Atlas, the data management and resource repository of the Extracellular RNA Communication Consortium, an NIH Pooled Fund project exploring the biology of exRNA.
In recent years, research has shown that RNA not only exists within cells, but is also exported from cells as extracellular RNA and plays a role in cell-to-cell communication.
“ExRNAs exist in body fluids outside of cells, where they can associate with a variety of transporters, including RNA-binding proteins (RBPs), but the loading and distribution of RBPs across the transporters is largely unknown.” biofluids,” said co-author Robert Fullem, a graduate student in the Milosavljevic Laboratory. “Our goal in this study was to fill that gap. This large gap in knowledge limited our understanding of the role of RBPs as exRNA carriers in human body fluids. Our findings open a new path toward understanding the biology of exRNA and provide new opportunities for the development of exRBP/exRNA liquid biopsy biomarkers.”
The investigators applied computational analyzes to identify exRBPs in plasma, serum, saliva, urine, and cerebrospinal fluid. The computational predictions were approximately 80% experimentally validated in both plasma and cell cultures in the laboratory, suggesting a high specificity for the computational method.
“With this information, we developed a map of candidate exRBPs and their exRNA loading in body fluids, broadening the landscape of potential biomarkers that can now be studied in liquid biopsies and used to track normal and disease processes,” said Milosavljevic. “We present this map as a resource available at no cost to the scientific community.”
Other contributors to this paper include co-authors Emily L. LaPlante and Alessandra Stürchler, David Chen, Anne C. Starner, Emmanuel Esquivel, Eric Alsop, Andrew R. Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark Gerstein , Roger P. Alexander, Matthew E. Roth, Jeffrey Franklin, Robert Coffey, Robert L. Raffai, Isabelle M. Mansuy, Stavros Stavrakis, Andrew deMello, Louise C. Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu , Jennifer Jones, Kendall Van Keuren-Jensen, and Eric Van Nostrand.
This publication was supported in part by the NIH Common Fund (1UG3TR002881-01, 1U54DA036134-01,1U54DA049098-01, 1U54DA049098-01S1, 1UH3TR002881, OT2OD030547-01S1, and 5UG3TR002881-02). Additional support was provided by CPRIT Scholar in Cancer Research grants RR200040, 4UH3CA241703-03, and a Swiss National Center of Competence (NCCR) in Research RNA & Disease grant.
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