|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3548-3554
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
Antonio Condino-Neto and
Peter E. Newburger
From the Department of Pediatrics and Center for Investigation in
Pediatrics, State University of Campinas Medical School, Campinas,
São Paulo, Brazil; and the Department of Pediatrics and Cancer
Center, University of Massachusetts Medical School, Worcester, MA.
X-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- ) 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- 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- 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-, showed a similar
improvement in splicing. We conclude that IFN- 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Foster, S. Hulme, M. Lovell, K. Reed, and P. Barrow
Stimulation of gp91 Phagocytic Oxidase and Reactive Oxygen Species in Neutrophils by an Avirulent Salmonella enterica Serovar Infantis Strain Protects Gnotobiotic Piglets from Lethal Challenge with Serovar Typhimurium Strain F98 without Inducing Intestinal Pathology
Infect. Immun.,
August 1, 2005;
73(8):
4539 - 4547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Thomas, S. Samanta, C. Wu, N. Berliner, and E. Fikrig
Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
Infect. Immun.,
January 1, 2005;
73(1):
208 - 218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Qiao, S. Prabhakar, A. Canova, Y. Hoshino, M. Weiden, and R. Pine
Posttranscriptional Inhibition of Gene Expression by Mycobacterium tuberculosis Offsets Transcriptional Synergism with IFN-{gamma} and Posttranscriptional Up-Regulation by IFN-{gamma}
J. Immunol.,
March 1, 2004;
172(5):
2935 - 2943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Foster, S. D. Hulme, and P. A. Barrow
Induction of Antimicrobial Pathways during Early-Phase Immune Response to Salmonella spp. in Murine Macrophages: Gamma Interferon (IFN-{gamma}) and Upregulation of IFN-{gamma} Receptor Alpha Expression Are Required for NADPH Phagocytic Oxidase gp91-Stimulated Oxidative Burst and Control of Virulent Salmonella spp.
Infect. Immun.,
August 1, 2003;
71(8):
4733 - 4741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ishibashi, T. Mizukami, S. Kanegasaki, L. Motoda, R. Kakinuma, F. Endo, and H. Nunoi
Improved superoxide-generating ability by interferon {gamma} due to splicing pattern change of transcripts in neutrophils from patients with a splice site mutation in CYBB gene
Blood,
July 15, 2001;
98(2):
436 - 441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Snyder, J. F. Waring, S. Z. Zhu, S. Kaplan, J. Schultz, and G. D. Ginder
A 3'-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-{{gamma}}
J. Immunol.,
March 15, 2001;
166(6):
3966 - 3974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-C. Yu, Y.-C. Twu, C.-Y. Chang, and M. Lin
Molecular Basis of the Kell-null Phenotype. A MUTATION AT THE SPLICE SITE OF HUMAN KEL GENE ABOLISHES THE EXPRESSION OF KELL BLOOD GROUP ANTIGENS
J. Biol. Chem.,
March 23, 2001;
276(13):
10247 - 10252.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
