RNA Operons in Coordinated Gene Expression and Horizontal Transfer

Duke University, Durham NC

Investigators

Abstract

Recent developments at the interface between cell and molecular biology suggest that membrane-bound particles called exosomes may serve as a vehicle to transmit genetic information through the extracellular milieu in mammals in the form of RNA-protein complexes. This is believed to occur via release of exosomes by one cell and subsequent uptake by neighboring cells, thereby providing a modular form of cell-cell communication. While a rudimentary understanding of the consequences of exosome mediated information transfer has begun to emerge, the organizing principles of the RNA-protein complexes contained within these particles remain to be elucidated. A likely possibility is that they correspond to RNA regulons, that is, modules of RNA and protein in which the RNAs are functionally related and thus comprise coherent packets of genetic information. Knowledge of exosome content and transmission will serve as a foundation for understanding the horizontal transfer of information at the level of RNA-protein complexes, which is dramatically different from the better understood vertical transfer of information through germ-line DNA. Broader Impacts: Understanding how information is transmitted from cell to cell in metazoan animals such as humans is fundamental to biology. Moreover, it has profound implications for the development of tissues, organs and ecosystems in which mixtures of cells and cell types improve their fitness and communal adaptation by reprogramming surrounding cells and thereby advancing the rate of evolution. Although RNA-mediated horizontal transfer of information is not yet included in textbooks at any level, the concepts surrounding RNA regulons and coherent information exchange among cells through exosome release and uptake are beginning to find their way into university courses and onto the internet. Under this award, the Keene laboratory will continue to integrate cutting edge research in this area with educational and training opportunities, thereby bringing novel ideas to young minds and stimulating the development of ideas through feedback and reinvestigation. Advances in the field of RNA-mediated horizontal transfer of genetic information will be included in outreach programs sponsored by Duke University, including those targeted to traditionally minority schools, in order to inform the next generation of students and teachers about this emerging field.