title: Identification of a novel transcript of X25, the human gene involved in Friedreich ataxia.
abstract: Friedreich ataxia (FRDA) is caused by a GAA triplet expansion in the first intron of the X25 gene. The X25 gene encodes a 210-amino acid protein, frataxin (A isoform). Here, we report the identification of a new transcript of the X25 gene generated by alternative splicing by the use of a second donor splice site in the intron 4. Full-length cDNA transcript sequence revealed an insertion of 8 bp between 4 and 5a exon sequence. This event leads to a frameshift in the mRNA reading frame and introduces a new stop codon at position 589. Therefore, this X25 transcript variant may encode a 196-amino acid protein, the A1 isoform, that structurally differs from the main A isoform of 210 amino acids after residue 160. In all human tissues analyzed, reverse transcription-polymerase chain reaction experiments demonstrated that the A1 isoform was expressed at low levels compared with the predominant A isoform. No difference in A and A1 isoform expression rate was detected between FRDA patients and normal controls. We did not find an A1 like splice variant in rodents.
authors.affiliation: BioGeM, c/o Department of Molecular and Cellular Biology and Pathology, Federico II University, Via S. Pansini, 580131 Naples, Italy. pianese@biogem.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Pianese
authors.forename: Angela
authors.initials: A
authors.lastname: Tammaro
authors.forename: Mimmo
authors.initials: M
authors.lastname: Turano
authors.forename: Irene
authors.initials: I
authors.lastname: De Biase
authors.forename: Antonella
authors.initials: A
authors.lastname: Monticelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D005621:Friedreich Ataxia / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D007438:Introns / Q000235:genetics; D033862:Iron-Binding Proteins; D051379:Mice; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000302:isolation & purification; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D000096923:Frataxin
chemical_list: D018388:Codon, Terminator; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D020033:Protein Isoforms; D000096923:Frataxin