Identification of a novel transcript of X25, the human gene involved in Friedreich ataxia

Neurosci Lett. 2002 Mar 8;320(3):137-40. doi: 10.1016/s0304-3940(02)00048-4.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Base Sequence / genetics
  • Codon, Terminator / genetics
  • DNA Mutational Analysis
  • Exons / genetics
  • Frameshift Mutation / genetics*
  • Frataxin
  • Friedreich Ataxia / genetics*
  • Friedreich Ataxia / metabolism
  • Genetic Testing
  • Humans
  • Introns / genetics
  • Iron-Binding Proteins*
  • Mice
  • Molecular Sequence Data
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / isolation & purification
  • Protein Isoforms / genetics
  • Protein Isoforms / isolation & purification
  • Rats
  • Sequence Homology, Amino Acid
  • Transcription, Genetic / genetics
  • Trinucleotide Repeat Expansion / genetics

Substances

  • Codon, Terminator
  • Iron-Binding Proteins
  • Protein Isoforms
  • Phosphotransferases (Alcohol Group Acceptor)