Role of NEAT1 lncRNA in HIV replication

NEAT1 lncRNA 在 HIV 复制中的作用

• 批准号: 9292251
• 负责人: Andrew P Rice
• 金额: $ 19.81万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-09 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9292251
• 关键词: Address; Affect; Biology; CCL19 gene; CD4 Positive T Lymphocytes; Cell Nucleus; Cell model; Cells; Chromatin; Cytoplasm; Data; Elements; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genome; HIV; HIV Infections; Human; Length; Maintenance; Maps; Mediating; Memory; Nuclear; Nuclear Export; Nuclear Structure; Pattern; Play; Poly A; Property; Proteins; Proviruses; RNA; RNA Polymerase II; RNA Splicing; Repression; Research; Rest; Role; Site; Small Interfering RNA; Spices; T-Cell Activation; T-Lymphocyte; Testing; Transcript; Transcription Initiation Site; Untranslated RNA; Untranslated Regions; Viral; Virus Latency; chromatin remodeling; innovation; insight; latent infection; mRNA Precursor; memory CD4 T lymphocyte; novel; promoter; rev Protein; scaffold; transcription termination; viral RNA

NEAT1_1 and NEAT1_2 are related long noncoding RNAs (lncRNAs) that accumulate to high levels in the nucleus. NEAT1 RNAs serve as essential scaffolds to assemble nuclear structures termed paraspeckles that contain approximately 45 proteins in addition to the lncRNAs. Recent findings indicate that incompletely spliced HIV RNAs are retained in the nucleus through an association with paraspeckles. Importantly, NEAT1 RNAs are expressed at high levels in resting CD4 T cells, and their levels are strongly down-regulated by T cell activation. This expression pattern suggests that NEAT1 RNAs function to retain viral transcripts in the nucleus of quiescent CD4 T cells. The proposed research will investigate whether the nuclear retention of viral RNAs by NEAT1 RNAs acts to repress HIV replication in resting CD4 T cells, as well as to maintain HIV latency in resting CD4 T cells. Additionally, paraspeckle proteins include several RNA splicing factors and chromatin remodeling proteins. The research will therefore also examine if NEAT1 RNAs play roles in HIV RNA splicing and proviral transcription by RNA Polymerase II. Completion of the proposed research is likely to provide new insight into mechanisms of HIV gene regulation and viral latency.

NEAT1_1和NEAT1_2是相关的长非编码RNA（lncRNA），其在细胞中积累到高水平。 原子核NEAT 1 RNA作为组装称为paraspeckles的核结构的基本支架， 除了lncRNA外还含有大约45种蛋白质。最近的研究结果表明，不完全 剪接的HIV RNA通过与旁斑的结合保留在细胞核中。重要的是，NEAT1 RNA在静息的CD4 T细胞中以高水平表达，并且它们的水平被T细胞免疫抑制剂强烈下调。 activation.这种表达模式表明NEAT 1 RNA的功能是将病毒转录物保留在细胞中。 静止的CD4 T细胞的细胞核。这项拟议中的研究将调查病毒的核滞留是否 NEAT1 RNA的作用是抑制HIV在静息CD4 T细胞中的复制，以及维持HIV 静息CD4 T细胞的潜伏期。此外，旁斑蛋白包括几种RNA剪接因子， 染色质重塑蛋白。因此，该研究还将研究NEAT1 RNA是否在HIV中发挥作用 通过RNA聚合酶II进行RNA剪接和前病毒转录。完成拟议的研究可能会 为HIV基因调控和病毒潜伏机制提供了新的见解。