title: Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with ichthyosis vulgaris.
abstract: Ichthyosis vulgaris (IV) is an inherited scaling skin disorder in which expression of profilaggrin is reduced. Previous studies have indicated that the reduction is caused by defective post-transcriptional control of gene expression. Here we present evidence that profilaggrin mRNA in keratinocytes cultured from subjects with IV is intrinsically unstable and has a shorter half-life compared with that in normal cells. When IV-affected keratinocytes were treated with the protein synthesis inhibitor cycloheximide, the steady-state level of profilaggrin mRNA was increased due to stabilization of the transcript. In addition, the number of filaggrin repeats within the profilaggrin gene was studied. The number of filaggrin repeats (10-12) in individuals with IV did not differ from that of unaffected subjects. Expression of the gene was bi-allelic and coequal in both control and affected individuals. Our results suggest a model in which a labile ribonuclease and a stabilizing factor may modulate the profilaggrin mRNA steady-state level in normal cells, whereas the stabilizing factor may be absent or functionally inactive in IV-affected keratinocytes.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195-6524, USA.
authors.forename: W
authors.initials: W
authors.lastname: Nirunsuksiri
authors.forename: S H
authors.initials: SH
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Fleckman
mesh_terms: D000483:Alleles; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000235:genetics; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D006207:Half-Life; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics* / Q000473:pathology*; D007381:Intermediate Filament Proteins / Q000187:drug effects / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000187:drug effects / Q000235:genetics*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D015534:Trans-Activators; D004247:DNA