The aim of the proposed research is to understand how small RNA structures can be recognized as a functional signal in various aspects of the viral life cycle. Previous studies suggested that viral RNA participates in many different viral mechanisms by not only using its sequence but also using its unique structure. In RNA viruses and retroviruses, specific regions of viral genomic RNA seem to assume important roles in various processes of their life cycle, including viral RNA replication, dimerization and encapsidation. For each process, relatively small, but unique RNA sequences have been identified as functional motifs that are likely to interact with proteins or other RNAs to conduct their biological functions. The proposed study will focus on structural characteristics of the RNA motifs that participate in RNA dimerization and replication processes. RNA motifs involved in RNA replication process seem to employ their unique secondary and tertiary structure as a recognition signal for a replicating enzyme complex. RNA motifs involved in RNA dimerization process have unique sequences that tend to form a loop-to-loop kissing complex and eventually an extended duplex. We are going to investigate conformational characteristics of these RNA motifs in the context of their biological functions, using high-resolution NMR spectroscopy and other useful biophysical and biochemical tools including UV melting and gel electrophoresis. Two different dimerizaton RNA motifs from Moloney Murine Leukemia Virus and Human T-cell Leukemia Virus will be studied in terms of their conformational characteristics, we will also investigate the high-resolution solution structures of two replication RNA motifs originating from Hepatitis C Virus and Cucumber Mosaic Virus. Our study will elucidate the structural origins of the interesting biological functions that these RNA motifs assume, which will contribute to the fundamental understanding of each viral mechanism. This will lead to the establishment of more effective anti-viral drug design strategy that targets important RNA motifs.
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