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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM048135-15
Application #
7629033
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
15
Fiscal Year
2008
Total Cost
$268,190
Indirect Cost
Name
California State University Hayward
Department
Type
DUNS #
194044335
City
Hayward
State
CA
Country
United States
Zip Code
94542
Chu, Wally; Weerasekera, Akila; Kim, Chul-Hyun (2017) On the conformational stability of the smallest RNA kissing complexes maintained through two G·C base pairs. Biochem Biophys Res Commun 483:39-44
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Barnes, Donna B; Murphy, Sheigla (2009) Reproductive decisions for women with HIV: motherhood's role in envisioning a future. Qual Health Res 19:481-91
Chen, Anna K; Hedrick, Michael S (2008) Role of glutamate and substance P in the amphibian respiratory network during development. Respir Physiol Neurobiol 162:24-31
Green, Lisa; Kim, Chul-Hyun; Bustamante, Carlos et al. (2008) Characterization of the mechanical unfolding of RNA pseudoknots. J Mol Biol 375:511-28
Hedrick, Michael S; Fahlman, Christian S; Bickler, Philip E (2005) Intracellular calcium and survival of tadpole forebrain cells in anoxia. J Exp Biol 208:681-6
Hedrick, Michael S (2005) Development of respiratory rhythm generation in ectothermic vertebrates. Respir Physiol Neurobiol 149:29-41
Winmill, Rachel E; Chen, Anna K; Hedrick, Michael S (2005) Development of the respiratory response to hypoxia in the isolated brainstem of the bullfrog Rana catesbeiana. J Exp Biol 208:213-22
Hedrick, Michael S; Chen, Anna K; Jessop, Kristy L (2005) Nitric oxide changes its role as a modulator of respiratory motor activity during development in the bullfrog (Rana catesbeiana). Comp Biochem Physiol A Mol Integr Physiol 142:231-40
Hedrick, Michael S; Winmill, Rachel E (2003) Excitatory and inhibitory effects of tricaine (MS-222) on fictive breathing in isolated bullfrog brain stem. Am J Physiol Regul Integr Comp Physiol 284:R405-12

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