Revealing the RNA-RNA interactome of the HIV-1 genome

揭示 HIV-1 基因组的 RNA-RNA 相互作用组

• 批准号: 10228084
• 负责人: William Anthony Cantara
• 金额: $ 19.5万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-03 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228084
• 关键词: Acylation; Affinity; Amino Acid Sequence; Antiviral Agents; Base Pairing; Binding; Binding Proteins; Biological; Biological Assay; Biological Testing; Cells; DNA; Data; Elements; Enzymes; Event; Evolution; Genetic Carriers; Genome; HIV Genome; HIV-1; Heterogeneity; Hydroxyl Radical; Infection; Integration Host Factors; Length; Ligation; Mediating; Methods; MicroRNAs; Modeling; Molecular Conformation; Mutagenesis; Mutate; Mutation; Nucleic Acids; Nucleotides; Oligonucleotides; Outcome; Participant; Play; Polyadenylation; Primer Extension; Process; RNA; RNA Binding; RNA Splice Sites; RNA Splicing; RNA Viruses; RNA annealing; RNA replication; Retroviridae; Reverse Transcription; Role; Structural Models; Structure; Testing; Transfer RNA; U1 Small Nuclear Ribonucleoprotein; U1 small nuclear RNA; U2 small nuclear RNA; Untranslated RNA; Validation; Virus; base; conformer; crosslink; deep sequencing; evidence base; experimental study; genetic information; genomic RNA; insight; new therapeutic target; novel; pressure; response; viral RNA

Project Summary/Abstract Retroviruses, like many RNA viruses, have high mutation rates, allowing rapid genome evolution to select for beneficial host factor interactions. Recently the importance of non-coding RNAs (ncRNAs) for host antiviral processes have been highlighted; however, many RNA viruses have also evolved to make use of host ncRNAs for their own benefit. Indeed, several microRNAs (miRNAs) have been identified that inhibit replication of mammalian RNA viruses while others increase replication. It is important to point out that repressed replication is likely to be advantageous to the virus in many instances. Furthermore, retroviruses are dependent on a host tRNA to prime reverse transcription of their genomic RNA (gRNA) into double-stranded proviral DNA. This fundamental tRNA-gRNA interaction precedes all enzyme-catalyzed processes during retroviral infection of a host cell. In addition, tRNA-derived fragments (tRFs) that result from endonucleolytic cleavage of tRNAs have recently been shown to inhibit endogenous retroviral replication by regulating reverse transcription. Due to the rapid response of HIV-1 to selective pressure, it is likely to have evolved mechanisms of responding to RNA- mediated host processes; however, comprehensive identification of the HIV-1 gRNA nucleic acid interactome is lacking. Here, we aim to test the overarching hypothesis that HIV-1 gRNA has evolved critical RNA-RNA interactions such as alternative conformations, long-range intra-molecular interactions and direct binding of host ncRNAs to optimize infectivity. The specific aims are to (1) identify HIV-1 gRNA intra-molecular base-pairing and inter-molecular host RNA interactions and (2) test the biological significance of HIV-1 RNA-RNA interactions.

项目总结/文摘