Two alternative promoters regulate the expression of lysinuric protein intolerance gene SLC7A7
| Autor: | Olli Simell, Juha Mykkänen, Kirsi Huoponen, Kirsi Puomila |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Molecular Sequence Data Biology Biochemistry Cell Line Mice Exon Endocrinology Species Specificity Sequence Homology Nucleic Acid Genetics medicine Animals Humans Coding region Tissue Distribution RNA Messenger Promoter Regions Genetic Amino Acid Metabolism Inborn Errors Molecular Biology Gene DNA Primers chemistry.chemical_classification Regulation of gene expression Base Sequence Fusion Regulatory Protein 1 Light Chains Amino Acid Transport System y+L Promoter medicine.disease TATA Box Molecular biology Lysinuric protein intolerance ta3123 Introns Rats SLC7A7 Gene Amino acid Gene Expression Regulation chemistry 5' Untranslated Regions |
| Zdroj: | Molecular Genetics and Metabolism. 90(3):298-306 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2006.11.007 |
| Popis: | The human SLC7A7 gene encodes y(+)L amino acid transporter-1 (y(+)LAT-1). Mutations in the SLC7A7 coding region cause a rare recessive disorder, lysinuric protein intolerance (LPI). LPI is enriched in the Finnish population, where all patients carry the same homozygous founder mutation. Although the same LPI genotype is present in all patients, clinical symptoms vary greatly and thus show no genotype-phenotype correlation. In LPI, the transport of cationic amino acids is functionally affected at least at the basolateral membrane of the polarised epithelial cells in the kidney tubules and small intestine, although SLC7A7 is expressed much more widely. Interestingly, some LPI patients' tissues exhibit normal cationic amino acid transport despite the mutations leading to clinical phenotype. When studying the various manifestations of this monogenic disorder and the tissue specificity of the transport defect, it is crucial to know the transcriptional regulatory mechanisms of SLC7A7 gene. In this study, we have identified a novel alternative, TATA-box-containing promoter that plays a role in the tissue-specific regulation of the SLC7A7 gene expression. This newly found downstream promoter in front of exon 2 seems to be active in tissues with strong defects in the function of the transporter in patients with LPI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect