Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation

dc.creatorCondino-Neto, A
dc.creatorNewburger, PE
dc.date2000
dc.date37043
dc.date2014-12-02T16:25:10Z
dc.date2015-11-26T16:12:53Z
dc.date2014-12-02T16:25:10Z
dc.date2015-11-26T16:12:53Z
dc.date.accessioned2018-03-28T23:00:51Z
dc.date.available2018-03-28T23:00:51Z
dc.identifierBlood. Amer Soc Hematology, v. 95, n. 11, n. 3548, n. 3554, 2000.
dc.identifier0006-4971
dc.identifierWOS:000087351600038
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60434
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/60434
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60434
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1267315
dc.descriptionX-linked chronic granulomatous disease (CGD) derives from defects in the CYBB gene, which encodes the gp91-phox component of NADPH oxidase. We studied the molecular basis of the disease in a kindred with variant CGD, due to a single base substitution at the sixth position of CYBB first intron. The patients' phagocytes have been shown previously to greatly increase superoxide release in response to interferon-gamma (IFN-gamma) in vitro and in vivo. We examined CYBB gene expression in an Epstein-Barr virus (EBV)-transformed B-cell line from 1 patient in this kindred. These cells showed markedly decreased levels of CYBB transcripts in total RNA (5% of normal) and nuclear RNA (1.4% of normal), despite equal CYBB transcription rates in the CGD and control cells. Incubation with IFN-gamma produced a 3-fold increase in CYBB total messenger RNA (mRNA) levels in the patient's cells, and decreased nuclear transcripts to undetectable levels. Reverse transcriptase-polymerase chain reaction analysis of RNA splicing revealed a preponderance of unspliced CYBB transcripts in the patient's nuclear RNA. In vitro incubation with IFN-gamma increased by 40% the ratio of spliced relative to unspliced CYBB mRNA in nuclei from the CGD B-cell line. Total RNA harvested from the same patient's monocytes, on and off therapy with IFN-gamma, showed a similar improvement in splicing. We conclude that IFN-gamma partially corrects a nuclear processing defect due to the intronic mutation in the CYBB gene in this kindred, most likely by augmentation of nuclear export of normal transcripts, and improvement in the fidelity of splicing at the first intron. (Blood. 2000;95:3548-3554) (C) 2000 by The American Society of Hematology.
dc.description95
dc.description11
dc.description3548
dc.description3554
dc.languageen
dc.publisherAmer Soc Hematology
dc.publisherWashington
dc.publisherEUA
dc.relationBlood
dc.relationBlood
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectTumor-necrosis-factor
dc.subjectMessenger-rna Stabilization
dc.subjectPhorbol-myristate Acetate
dc.subjectCytochrome-b Heavy
dc.subjectNadph Oxidase
dc.subjectRespiratory-burst
dc.subjectLight Chain
dc.subjectCell Lines
dc.subjectExpression
dc.subjectComponents
dc.titleInterferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation
dc.typeArtículos de revistas


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