RNAMEDTGS

RNA-mediated Transcriptional Gene Silencing in Humans

 Coordinatore CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE 

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 Nazionalità Coordinatore France [FR]
 Totale costo 1˙999˙974 €
 EC contributo 1˙999˙974 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-CoG
 Funding Scheme ERC-CG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-03-01   -   2019-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

 Organization address address: Rue Michel -Ange 3
city: PARIS
postcode: 75794

contact info
Titolo: Dr.
Nome: Rosemary Elizabeth
Cognome: Kiernan
Email: send email
Telefono: +33 434359974
Fax: +33 434359901

FR (PARIS) hostInstitution 1˙999˙974.00
2    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

 Organization address address: Rue Michel -Ange 3
city: PARIS
postcode: 75794

contact info
Titolo: Mr.
Nome: Jocelyn
Cognome: Mere
Email: send email
Telefono: +33 4 67613535
Fax: +33 4 67043236

FR (PARIS) hostInstitution 1˙999˙974.00

Mappa

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 Word cloud

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expression    tar    microprocessor    genome    coupled    xrn    global    molecular    small    transcription    humans    human    termination    premature    hiv    gene    ltr    tgs    rrp    mediated    rna    rnapii    evidence    transcriptional    mechanism   

 Obiettivo del progetto (Objective)

'More than 70% of the human genome synthesizes non-coding RNA that is believed to regulate gene expression. While there is ample evidence from model systems that small RNAs are the lynchpin of powerful mechanisms that silence transcription, the demonstration of transcriptional gene silencing (TGS) mediated by a small RNA in humans is lacking. We have recently shown that the HIV-1 LTR is controlled by premature termination of transcription and TGS mediated by a small RNA derived from the stem-loop structure, TAR, that forms the 5’ end of HIV-1 transcripts. This pathway depends on Microprocessor, Xrn2, Setx and Rrp6. Cleavage of TAR by Microprocessor has major consequences 1) it provides a substrate for Rrp6, which generates a small RNA that represses HIV-1 transcription, 2) it creates an entry site for Xrn2 and termination factors that lead to premature termination of transcription. Loss of Microprocessor or Rrp6 leads to recruitment of RNAPII to the LTR and activation of transcription. These findings not only provide the first evidence showing that small RNA-mediated TGS acts in human cells, but they also uncovered a new mechanism of gene regulation involving premature termination of transcription by RNAPII. Several important questions now need to be answered. What is the mechanism underlying small RNA-mediated TGS? Does small RNA-mediated TGS operate at human genes? What is the contribution of TGS coupled to premature termination in the global control of transcription? We will use a battery of biochemical and molecular approaches to dissect the molecular mechanism of RNA-mediated TGS. The global importance of small RNA-mediated TGS and premature termination of transcription in the control of human gene expression will be addressed using complementary genome-wide approaches. RNA-mediated TGS coupled to premature termination, if confirmed as a widespread mechanism controlling transcription, will fundamentally change our perspective of transcriptional control in humans'

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