Our understanding of the structure, function, and evolution of RNA molecules has increased significantly with the recent improvements in sequencing and crystallography. The accuracy and detail that can be deciphered from RNA data are directly proportional to the creativity, design, and speed of the analysis, as well the organization and accessibility of the data. Over the past 25 years, the Gutell Lab has successfully developed sequence and structure analysis techniques and associated data management systems, producing an accurate prediction of Ribosomal RNA secondary structure and the identification and characterization of new structural motifs. In parallel, they have disseminated large amounts of comparative sequence and structure information to the scientific community from their Comparative RNA Web (CRW) Site. The CRW Project, funded by the NIH, is used by many laboratories to further their research on RNA structure and evolution. Due to significant increases in the amount of RNA sequence information, high-resolution crystal structures for the RNA molecules of interest, and the greater appreciation for the structure and evolution of these molecules when comparative sequence data and high-resolution structures are analyzed simultaneously, they have begun developing a new SQL Server based comparative analysis system to accommodate more than 500,000 sequences, base pair and other comparative structure information for all of the sequences, and crystal structure coordinates, while associating every sequence onto the NCBI phylogenetic tree of life. This new system is the foundation for more far-reaching comparative structural and evolutionary studies, and the dynamic creation of data. A new secondary structure java applet is being developed that will enhance the navigation of the RNA secondary structure and three-dimensional structure and establish an interface for dynamic access, creation, and discovery of comparative structure, structural motif, and high-resolution crystal structure information.7. PROJECT NARRATIVE An understanding of the molecular structure of the cell is providing us with a better appreciation for the cellular functions. RNA, one of the major components of the cell, is now being associated with vital structural and functional roles in the cell. The comparative studies of RNA are revealing accurate and detailed structural information while providing an important evolutionary perspective that is useful in the design of new drug therapies.