Human Na(+)-myo-inositol cotransporter gene: alternate splicing generates diverse transcripts
| Autor: | Masaki Togawa, Martin J. Stevens, Dennis Larkin, Francesca Porcellati, Douglas A. Greene, Thomas W. Glover, Yoshiyuki Hosaka, Tommy Hlaing, Douglas N. Henry, Paul D. Killen |
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| Rok vydání: | 1998 |
| Předmět: |
DNA
Complementary Transcription Genetic Physiology Molecular Sequence Data Biology chemistry.chemical_compound Dogs medicine Animals Humans Inositol Amino Acid Sequence Cloning Molecular Gene Heat-Shock Proteins Kidney Base Sequence Symporters Alternative splicing Chromosome Mapping Membrane Proteins Cell Biology Exons Epithelium Alternative Splicing medicine.anatomical_structure chemistry Biochemistry Osmoregulation RNA Cotransporter Carrier Proteins Intracellular |
| Zdroj: | The American journal of physiology. 274(5) |
| ISSN: | 0002-9513 |
| Popis: | Na+- myo-inositol cotransport activity generally maintains millimolar intracellular concentrations of myo-inositol and specifically promotes transepithelial myo-inositol transport in kidney, intestine, retina, and choroid plexus. Glucose-induced, tissue-specific myo-inositol depletion and impaired Na+- myo-inositol cotransport activity are implicated in the pathogenesis of diabetic complications, a process modeled in vitro in cultured human retinal pigment epithelium (RPE) cells. To explore this process at the molecular level, a human RPE cDNA library was screened with a canine Na+-dependent myo-inositol cotransporter (SMIT) cDNA. Overlapping cDNAs spanning 3569 nt were cloned. The resulting cDNA sequence contained a 2154-nt open reading frame, 97% identical to the canine SMIT amino acid sequence. Genomic clones containing SMIT exons suggested that the cDNA is derived from at least five exons. Hypertonic stress induced a time-dependent increase, initially in a 16-kb transcript and subsequently in 11.5-, 9.8-, 8.5-, 3.8-, and ∼1.2-kb SMIT transcripts, that was ascribed to alternate exon splicing using exon-specific probes and direct cDNA sequencing. The human SMIT gene is a complex multiexon transcriptional unit that by alternate exon splicing generates multiple SMIT transcripts that accumulate differentially in response to hypertonic stress. |
| Databáze: | OpenAIRE |
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