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3DviralRNA

Structural and functional characterization of large viral and human non-coding RNA motifs involved in HIV infection

Total Cost €

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EC-Contrib. €

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Partnership

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 3DviralRNA project word cloud

Explore the words cloud of the 3DviralRNA project. It provides you a very rough idea of what is the project "3DviralRNA" about.

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Project "3DviralRNA" data sheet

The following table provides information about the project.

Coordinator
EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 159˙460.00

Map

 Project objective

HIV infections cause 1.2Mi deaths/year worldwide at steadily-increasing rates, partly because of antiretroviral resistance and the impossibility of eradicating latent viruses. To expand our understanding of HIV pathogenesis, we need to unravel all molecular mechanisms involved in HIV progression. Large viral and human RNAs are emerging as key players in HIV infection. To characterize such RNAs, I will employ an integrated structural biology approach complemented by biochemical and functional assays in vitro and in vivo and I will address two fundamental questions: 1. How does the structure of HIV genomic RNA regulate HIV infectivity? HIV genomic RNA regulates nuclear export, packaging, splicing, and translation of viral proteins. 3D structures are known for short motifs (<200 nt), e.g. TAR and RRE. Such motifs are part of 11 larger domains (>400 nt), whose structures are unknown but conserved across HIV strains suggesting functional importance. We will study domain 2 (450 nt), which encompasses the gag-pol frameshifting motif and is crucial for correct protein synthesis. Our work will offer unprecedented insights into the structural complexity of the genome of an RNA virus. 2. How does the structure of human long non-coding RNAs (lncRNAs) affect the host-cell response to HIV infection? HIV infections alter expression of human lncRNAs, e.g. HOTAIR, which regulate Polycomb chromatin remodeling enzymes, e.g. PRC1/PRC2, favoring epigenetic silencing and latency of HIV genes. Interactions between HOTAIR and PRC1/PRC2 are not well characterized at the molecular level. We will study HOTAIR domain 1 (530 nt), which interacts with PRC1/PRC2 and regulates their cellular action. Such work will reveal novel mechanisms of epigenetic gene-silencing that induce HIV latency. By revealing molecular details of HIV and human RNAs, our study will enrich our understanding of HIV infectivity, potentially opening new ways for future therapies against RNA viruses.

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