Skip to Main content Skip to Navigation
Journal articles

G-quadruplex structures in TP53 intron 3: role in alternative splicing and in production of p53 mRNA isoforms

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

https://hal-mnhn.archives-ouvertes.fr/mnhn-02619085
Contributor : Phong Lan Thao Tran <>
Submitted on : Monday, May 25, 2020 - 4:12:31 PM
Last modification on : Wednesday, October 14, 2020 - 3:45:46 AM

Links full text

Identifiers

Collections

Citation

Phong Lan Thao Tran, Antonella Virgilio, Veronica Esposito, Giuseppe Citarella, Aldo Galeone, et al.. G-quadruplex structures in TP53 intron 3: role in alternative splicing and in production of p53 mRNA isoforms. Carcinogenesis, Oxford University Press (OUP), 2011, 32 (3), pp.271-278. ⟨10.1093/carcin/bgq253⟩. ⟨mnhn-02619085⟩

Share

Metrics

Record views

8