Rna Protein Interactions In The Post Transcriptional Regulation Of Retroviruses PDF Download

Abstract: Retroviruses are etiological agents of several human and animal immunosuppressive disorders. They are associated with certain types of cancer and are useful tools for gene transfer applications. All retroviruses encode a single primary transcript that encodes a complex proteome. The RNA genome is reverse transcribed into DNA, integrated into the host genome, and uses host cell factors to transcribe, process and traffic transcripts that encode viral proteins and act as virion precursor RNA, which is packaged into the progeny virions. The functionality of retroviral RNA is governed by ribonucleoprotein (RNP) complexes formed by host RNA helicases and other RNA-binding proteins. The 5' leader of retroviral RNA undergoes alternative inter- and intra-molecular RNA-RNA and RNA-protein interactions to complete multiple steps of the viral life cycle. Retroviruses do not encode any RNA helicases and are dependent on host enzymes and RNA chaperones. Several members of the host RNA helicase superfamily are necessary for progressive steps during the retroviral replication. RNA helicase A (RHA) interacts with the redundant structural elements in the 5' untranslated region (UTR) of retroviral and selected cellular mRNAs and this interaction is necessary to facilitate polyribosome formation and productive protein synthesis. The research presented in this dissertation has: (1) outlined the approaches to define the function of host RNA helicases in viral replication, (2) determined that the ATPase-dependent helicase function of RHA is necessary for HIV-1 translation, (3) determined that the RHA chaperone function promotes efficient morphogenesis of infectious HIV-1, and (4) identified a novel viral strategy to sustain HIV-1 proteins synthesis during downregulation of eIF4E-dependent translation initiation by HIV-1. In summary, the functionality of HIV-1 RNA is governed in part by RNP complexes formed by host RNA-binding proteins. Interaction with these host factors facilitate RNA:RNA and RNA:protein interactions thereby making the HIV-1 RNPs dynamic in nature. Dynamic changes in the RNP complexes are necessary for efficient viral protein synthesis, trafficking and morphogenesis of progeny virions that productively infect host lymphocytes to complete the viral life cycle.