2023-04-22 15:13:27
An international team led by researchers at Baylor College of Medicine with the National Institutes of Health Extracellular RNA Communication Consortium and the Bogdan Mateescu Laboratory at ETH Zürich and the University of Zürich has developed a powerful new resource for studying RNA extracellular (exRNA), a novel form of cell-to-cell communication. The study, published in the journal Cell genomicslays the groundwork for examining how exRNA and its carrier proteins found in body fluids function in healthy and diseased environments, potentially providing a means to accurately implement early detection and monitor disease processes.
“Ribonucleic acid or RNA is a type of genetic material found inside all living cells. It is best known for acting as a messenger carrying instructions encoded in DNA for protein synthesis,” said corresponding co-author Dr. Aleksandar. Milosavljevic, professor and holder of the Henry and Emma Meyer Chair in Molecular Genetics at Baylor. He is also Director of the Graduate Program in Quantitative and Computational Biosciences and a Fellow 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 exRNA biology.
In recent years, research has shown that RNA not only exists inside cells, but is also exported from cells as extracellular RNA and plays a role in intercellular 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 cargo and distribution of RBPs through biofluids are largely unknown,” said co-author Robert Fullem, a graduate student in Milosavljevic’s lab. “Our goal in this study was to fill this gap. This major knowledge gap has limited our understanding of the role of RBPs as exRNA carriers in human body fluids. Our findings open a new avenue towards understanding exRNA biology and provide new opportunities for the development of exRBP/exRNA liquid biopsy biomarkers.
The researchers applied computational analyzes to identify exRBPs in plasma, serum, saliva, urine and cerebrospinal fluid. Computational predictions have been approximately 80% validated experimentally in laboratory plasma and cell cultures, suggesting high specificity for the computational method.
“With this information, we have developed a map of candidate exRBPs and their exRNA cargo in body fluids, expanding the landscape of potential biomarkers that can now be studied in liquid biopsies and used to track normal and pathological processes.” , Milosavljevic said. “We present this map as a freely available resource to the scientific community.”
Other contributors to this work include co-first 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 grant from the Swiss National Center of Competence (NCCR) in RNA and Disease Research.
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