Function of Conserved Structures in Related Coliphage RNA's

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Jacobson 9316501 Dr. Jacobson and coworkers study the shape of large genomic RNAs in the RNA coliphage system. These molecules have a dual function: they carry the genetic information coding for viral genes; and in addition, hydrogen bonding between distant regions of the molecules regulate viral growth, controlling both the expression of viral proteins and viral RNA replication. The detailed conformation of the molecules will be studied in order to understand the structural mechanisms used in regulation. Electron microscopy is used as a primary tool. This method allows one to see large structural features in the RNA and to measure changes in the shape and relative stability of these structures in mutant RNAs that have been created by genetic engineering. The structural changes that are observed can be correlated with changes in the growth patterns of mutant viruses. The current work focuses on the conformation of genomic RNA from coliphage QB. Dr. Jacobson's studies demonstrated for the first time that the molecules contain two types of structural domains. One type is unusually stable; the other is highly variable and can switch between alternative conformations. Both types of structures appear to be utilized in the regulation of viral protein synthesis. Two of the stable domains appear to suppress translational initiation of viral proteins. In addition, stable domains may serve as structural anchors (much like door hinges) that limit the formation of alternative structures in the variable regions of the molecule. In addition, computer modeling will be used to understand RNA conformation. A new method was developed to detect likely stable structures as well as likely variable regions of an RNA molecule. The results obtained by modeling are consistent with electron microscopic studies with both native and mutant RNAs. The new approach is of general interest and will be used by investigators in many disciplines. %%% Many unanswered questions remain about the rol e of RNA structure in gene regulation in RNA coliphages. These can now be addressed with modern methods of analysis. Answers to these questions will provide fundamental insights into the properties of all large mRNA molecules, and are therefore relevant in understanding mechanisms governing growth, evolution, and the regulation of gene expression in disease causing plant and animal viruses. ***