Murine leukemia virus (MuLV), is a member of the type C retrovirus family. One of the characteristic features of the retroviruses is that each virion contains a dimer of two identical copies of (+) sense single stranded viral genomic RNA non-covalently joined near their 5' ends. The region of viral RNA through which they form the dimer structure is called the dimer linkage site and it involves certain structured sequences located at the psi-element of viral RNA. The psi-element of viral RNA is needed for proper encapsidation of the viral genetic material and encompasses the 5' end region of viral genomic RNA, beginning downstream from the primer binding site and extending into the 5' gag-coding region. Thus intracellular dimerization of retroviral RNA may be a key step in viral RNA encapsidation and production of infectious virions. Most of the retroviral RNA dimerization studies have been carried out using subgenomic viral RNA fragments in vitro. In the proposed investigation, we plan to study the intracellular retroviral RNA dimerization utilizing our hammerhead ribozyme mediated in vivo dimerization monitoring system. The overall objective of the project is to understand the precise mechanism of retroviral RNA dimerization in vivo and its relationship to viral packaging. Such study may provide important information regarding the sequence and structural features of retroviral DNA dimerization domain and may be highly useful in developing intracellular targeting strategies for trans-acting ribozymes in other retroviral systems such as human immunodeficiency virus (HIV-1).
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