Conferences 2016

Conférence GIRC
Grenoble Institute for Cancer Research
Tuesday 12 January
Khelifa Arab
DKFZ, Heidelberg
IAB Conference room 11 am
Long non-coding RNA targets DNA
Non-coding RNAs are a large diversified family of transcripts, which can be classified by:
size, function or cellular localization. Although lowly conserved between species, long noncoding RNAs (lncRNAs) exhibit cell- and tissues-specific expression even more so than
messenger RNAs, suggesting functions in cell fate decision. LncRNA emerged recently as
key players in epigenetic reprogramming and genome regulation. However for many
lncRNAs their function are still unknown. We have discovered and characterized a lncRNA
termed TARID (Transcription Factor 21 antisense RNA inducing demethylation). TARID is a
TCF21 antisense lncRNA that reactivates the tumor suppressor TCF21 by repressing aberrant
promoter DNA methylation and promoting a permissive chromatin state. TARID interacts
physically with TCF21 promoter and triggers the targeting of the DNA demethylation
machinery via GADD45a (Growth arrest and DNA-damage inducible alpha). The dynamic
process of TCF21 promoter DNA demethylation requires a DNA repair step after TET (Teneleven translocation methylcytosine dioxygenase 1) mediated oxidation of 5-methylcytosine.
The base excision repair machinery involving TDG (thymine DNA glycosylase) removes
oxidized 5-methylcytosine bases and repairs the lesions by unmethylated cytosines. We
conclude that TARID is serving as an adapter to link the DNA demethylation complex and
target the proteins specifically to TCF21 promoter sequences. Our results rises a novel
hypothesis that lncRNA may serve as genomic address labels to target the DNA
demethylation machinery to specific gene loci. Taken together, our work put lights on the
mechanisms of gene inactivation/reactivation during tumor development.
Invited by Pierre Hainaut
Grenoble Institut Recherche Cancer : Institut Albert Bonniot, Institut de Recherches en
Technologies et Sciences pour le
Vivant, Institut de Biologie Structurale, Grenoble Institut Neurosciences
Rond Point de La Chantourne, 38700 La Tronche (tram line B, stop: Grand Sablon)
The seminar is followed by discussions and exchanges with the speaker and a sandwich buffet is offered.