%0 Journal Article %T G-quadruplex structures in TP53 intron 3: role in alternative splicing and in production of p53 mRNA isoforms %+ University of Naples Federico II = Università degli studi di Napoli Federico II %+ University of Pennsylvania %+ Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) %+ Génotoxicologie, signalisation et radiothérapie expérimentale %+ Chimie des interactions moléculaires (CIM) %+ Centre for Ecology and Hydrology [Monks Wood] (CEH) %+ Institut Européen de Chimie et Biologie (IECB) %+ Sect Mech Carcinogenesis %A Thao Tran, Phong Lan %A Virgilio, Antonella %A Esposito, Veronica %A Citarella, Giuseppe %A Galeone, Aldo %A Tran, Phong %A Dyck, Eric, Van %A Marcel, Virginie %A Tran, Phong L.T. %A Sagne, Charlotte %A Martel-Planche, Ghyslaine %A Vaslin, Laurence %A Teulade-Fichou, Marie-Paule %A Hall, Janet %A Mergny, Jean-Louis %A Hainaut, Pierre %A van Dyck, Eric %< avec comité de lecture %@ 0143-3334 %J Carcinogenesis %I Oxford University Press (OUP) %V 32 %N 3 %P 271-278 %8 2011-03-01 %D 2011 %R 10.1093/carcin/bgq253 %Z Life Sciences [q-bio]/Biochemistry, Molecular BiologyJournal articles %X The tumor suppressor gene TP53, encoding p53, is expressed as several transcripts. The fully spliced p53 (FSp53) transcript encodes the canonical p53 protein. The alternatively spliced p53I2 transcript retains intron 2 and encodes D40p53 (or DNp53), an isoform lacking first 39 N-terminal residues corresponding to the main transactivation domain. We demonstrate the formation of G-quad-ruplex structures (G4) in a GC-rich region of intron 3 that modulates the splicing of intron 2. First, we show the formation of G4 in synthetic RNAs encompassing intron 3 sequences by ultraviolet melting, thermal difference spectra and circular dichroism spec-troscopy. These observations are confirmed by detection of G4-induced reverse transcriptase elongation stops in synthetic RNA of intron 3. In this region, p53 pre-messenger RNA (mRNA) contains a succession of short exons (exons 2 and 3) and introns (introns 2 and 4) covering a total of 333 bp. Site-directed mutagenesis of G-tracts putatively involved in G4 formation decreased by $30% the excision of intron 2 in a green fluorescent protein-reporter splicing assay. Moreover, treatment of lymphoblastoid cells with 360A, a synthetic ligand that binds to single-strand G4 structures, increases the formation of FSp53 mRNA and decreases p53I2 mRNA expression. These results indicate that G4 structures in intron 3 regulate the splicing of intron 2, leading to differential expression of transcripts encoding distinct p53 isoforms. %G English %L mnhn-02619085 %U https://mnhn.hal.science/mnhn-02619085 %~ MNHN %~ CNRS %~ UNIV-LYON1 %~ FNCLCC %~ CURIE %~ PSL %~ CRCL %~ UDL %~ UNIV-LYON %~ INSTITUT-CURIE-PSL %~ ALLIANCE-SU %~ TEST3-HALCNRS