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Functions of circular RNAs generated from backsplicing of the HIV-1 primary transcript

Functions of circular RNAs generated from backsplicing of the HIV-1 primary transcript
HIV-1初级转录物反向剪接产生的环状RNA的功能
批准号:
10481143
负责人:
MASSIMO CAPUTI
金额:
$22.88万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-01 至 2024-08-31

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英文摘要
PROJECT SUMMARY Circular RNAs (circRNAs) are a family of non-coding RNAs that originate from a non-canonical splicing event, named backsplicing, in which the upstream and downstream splicing sites of an RNA transcript become covalently linked to form a closed loop of RNA as opposed to the typical linear structure of mRNA transcripts. Cellular circRNAs play a role in development, cell differentiation, proliferation and are associated with cancer, neurological disorders, autoimmune and cardiovascular disease. circRNAs act as miRNAs sponges, thus inhibiting their function, and by interacting with RNA binding proteins (RBPs), modulating their availability, localization and activity. A few circRNAs have been also shown to modulate transcription and can be translated into short proteins. CircRNAs of viral origin have been identified in DNA viruses from the Herpesviridae and Papillomaviridae families. These viral circRNAs have been shown to promote cell proliferation and metastasis by acting as sponges for miRNAs with functions in tumor suppression. To date, no circRNA encoded by an RNA virus has been characterized. Analysis of the complex HIV-1 splicing pattern revealed that this virus has the potential to generate at least 15 distinct circRNAs. We designed several sets of divergent PCR primers to specifically amplify the predicted HIV circRNA isoforms. Divergent primers were designed to extend in opposite directions on templates from linear transcripts but extend towards each and amplify circularized transcripts. We were able to amplify and confirm by sequencing 15 distinct circRNA isoforms generated from backsplicing of the viral pre-mRNA. Given the long half-life of circRNAs (4-5 times the one of linear RNAs) it is plausible that HIV derived circRNAs modulate viral replication and infection by conditioning the infected cells. In this study we propose to define the precise amount and composition of the circular RNA molecules produced by the virus in primary T cells and a HIV latency model utilizing a combination of circRNA isoform specific qPCR and RNA Sequencing assays. We will also determine the role of the HIV-1 circRNAs in viral replication utilizing both, gain and loss of functions assays.
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Inhibition of HIV-1 replication by delivery of the SRSF1 RNA Recognition Motifs
  • 批准号:
    8993337
  • 项目类别:
  • 资助金额:
    $44.85万
  • 财政年份:
    2015
  • 负责人:
    MASSIMO CAPUTI
  • 依托单位:
hnRNP A1 inhibition of HIV-1 replication
  • 批准号:
    8140976
  • 项目类别:
  • 资助金额:
    $43.35万
  • 财政年份:
    2011
  • 负责人:
    MASSIMO CAPUTI
  • 依托单位:
Regulation of HIV-1 RNA Processing
  • 批准号:
    6989731
  • 项目类别:
  • 资助金额:
    $32.51万
  • 财政年份:
    2002
  • 负责人:
    MASSIMO CAPUTI
  • 依托单位:
Regulation of HIV-1 RNA Processing
  • 批准号:
    6591090
  • 项目类别:
  • 资助金额:
    $28.26万
  • 财政年份:
    2002
  • 负责人:
    MASSIMO CAPUTI
  • 依托单位:
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