Most Friedriech's Ataxia patients are homozygous for large expansions of a GAA triplet repeat tract within the first intron of the human FRDA gene on chromosome 9. As a result, the synthesis of the mRNA coding for an ubiquitous protein - frataxin, is markedly reduced. Frataxin is mainly located in the mitochondria. Although its precise cellular role is not known, it is clear that several mitochondrial functions are affected in patient cells, including respiration, iron–sulfur cluster assembly, iron homeostasis, and maintenance of the redox status. Mitochondrial dysfunction and oxidative damage are at the origin of the neurodegenerative tract of this disease. Three splicing isoforms are known for the frataxin gene. The major transcript (isoform 1) codes for a 210 aminoacid-protein, the other transcripts differ in their 3' terminus and are shorter (171 and 196 aminoacids, respectively). Apart from the initial discovery, the scientific literature reports very little about these splice variants. Taking advantage of the fact that frataxin is ubiquitous and may be studied in circulating mononuclear cells, we evaluated the relative amount of the three mRNA isoforms in 5 Friedriech's Ataxia patients and in 5 healthy subjects. Total amount of messenger mRNA coding for frataxin increased in both patients and controls following a two-month supplementation of tocotrienol (5 mg/kg body weight/die), however the increase was not the same for the three isoforms. The study, carried out mostly by RT-qPCR, was accompanied by the bioinformatic evaluation of the characteristics of the minor protein isoforms, in the attempt to understand their possible roles.
Frataxin mRNA abundance and their isoforms in Friedriech's VAtaxia patients and in normal subjects; effect of tocotrienol supplementation
BOLOTTA, ALESSANDRA;ABRUZZO, PROVVIDENZA MARIA;MARCHIONNI, COSETTA;CASADIO, RITA;MARINI, MARINA
2011
Abstract
Most Friedriech's Ataxia patients are homozygous for large expansions of a GAA triplet repeat tract within the first intron of the human FRDA gene on chromosome 9. As a result, the synthesis of the mRNA coding for an ubiquitous protein - frataxin, is markedly reduced. Frataxin is mainly located in the mitochondria. Although its precise cellular role is not known, it is clear that several mitochondrial functions are affected in patient cells, including respiration, iron–sulfur cluster assembly, iron homeostasis, and maintenance of the redox status. Mitochondrial dysfunction and oxidative damage are at the origin of the neurodegenerative tract of this disease. Three splicing isoforms are known for the frataxin gene. The major transcript (isoform 1) codes for a 210 aminoacid-protein, the other transcripts differ in their 3' terminus and are shorter (171 and 196 aminoacids, respectively). Apart from the initial discovery, the scientific literature reports very little about these splice variants. Taking advantage of the fact that frataxin is ubiquitous and may be studied in circulating mononuclear cells, we evaluated the relative amount of the three mRNA isoforms in 5 Friedriech's Ataxia patients and in 5 healthy subjects. Total amount of messenger mRNA coding for frataxin increased in both patients and controls following a two-month supplementation of tocotrienol (5 mg/kg body weight/die), however the increase was not the same for the three isoforms. The study, carried out mostly by RT-qPCR, was accompanied by the bioinformatic evaluation of the characteristics of the minor protein isoforms, in the attempt to understand their possible roles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
