Linked Life Data

7493028

Source:http://linkedlifedata.com/resource/pubmed/id/7493028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-1-11
pubmed:abstractText
The synthesis of ferritin, the iron-storing molecule, is regulated at the translational level by iron through interaction between a cytoplasmic protein, iron regulatory protein (IRP), and a conserved nucleotide motif present in the 5' non-coding region of all ferritin mRNAs--the iron responsive element (IRE). This region forms a stem-loop structure and when the supply of iron to the cells is limited, the IRP is bound to IRE and represses ferritin synthesis. Ferritin is composed of a 24-subunit protein shell surrounding an iron core. The two types of subunit, H and L, are encoded by two genes located on chromosomes 11q13 and 19q13.1, respectively. Both genes are ubiquitously expressed but transcriptional regulation mediates tissue-specific changes in the H/L mRNA ratio and isoferritin profiles. We now report the identification of a single point mutation in the IRE of the L-ferritin mRNA in members from a family affected with dominantly inherited hyperferritinaemia and cataract. This mutation consists of an A to G change in the highly conserved CAGUGU motif that constitutes the IRE loop and mediates the high-affinity interaction with the IRP. We show that this mutation abolishes the binding of IRP in vitro and leads to a high constitutive, poorly regulated L-ferritin synthesis in cultured lymphoblastoid cells established from affected patients. This is, to our knowledge, the first mutation affecting the IRP-IRE interaction and the iron-mediated regulation of ferritin synthesis. We suggest that excess production of ferritin in tissues is responsible for the hyperferritinaemia and that intracellular accumulation of ferritin leads to cataract.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
444-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract.
pubmed:affiliation
INSERM U409, Faculté Xavier Bichat, Paris, France.
pubmed:publicationType
Journal Article