scholarly journals Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing.

1993 ◽  
Vol 268 (3) ◽  
pp. 2268
Author(s):  
C.A. Johnson ◽  
P. Densen ◽  
R.K. Hurford ◽  
H.R. Colten ◽  
R.A. Wetsel
1992 ◽  
Vol 267 (13) ◽  
pp. 9347-9353
Author(s):  
C.A. Johnson ◽  
P Densen ◽  
R K Hurford ◽  
H.R. Colten ◽  
R.A. Wetsel

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wen-juan Li ◽  
Yao-hui He ◽  
Jing-jing Yang ◽  
Guo-sheng Hu ◽  
Yi-an Lin ◽  
...  

AbstractNumerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation. We find that PRMT7 predominantly methylates a glycine and arginine motif; multiple PRMT7-regulated arginine methylation sites are close to phosphorylations sites; methylation sites and proximal sequences are vulnerable to cancer mutations; and methylation is enriched in proteins associated with spliceosome and RNA-related pathways. We show that PRMT4/5/7-mediated arginine methylation regulates hnRNPA1 binding to RNA and several alternative splicing events. In breast, colorectal and prostate cancer cells, PRMT4/5/7 are upregulated and associated with high levels of hnRNPA1 arginine methylation and aberrant alternative splicing. Pharmacological inhibition of PRMT4/5/7 suppresses cancer cell growth and their co-inhibition shows synergistic effects, suggesting them as targets for cancer therapy.


1998 ◽  
Vol 80 (09) ◽  
pp. 376-381 ◽  
Author(s):  
W. Lissens ◽  
S. Seneca ◽  
P. Capel ◽  
B. Chatelain ◽  
P. Meeus ◽  
...  

SummaryThe molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed.DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intronexon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Georgios I. Laliotis ◽  
Adam D. Kenney ◽  
Evangelia Chavdoula ◽  
Arturo Orlacchio ◽  
Abdul Kaba ◽  
...  

AbstractAKT-phosphorylated IWS1 promotes Histone H3K36 trimethylation and alternative RNA splicing of target genes, including the U2AF65 splicing factor-encoding U2AF2. The predominant U2AF2 transcript, upon IWS1 phosphorylation block, lacks the RS-domain-encoding exon 2, and encodes a protein which fails to bind Prp19. Here we show that although both U2AF65 isoforms bind intronless mRNAs containing cytoplasmic accumulation region elements (CAR-E), only the RS domain-containing U2AF65 recruits Prp19 and promotes their nuclear export. The loading of U2AF65 to CAR-Elements was RS domain-independent, but RNA PolII-dependent. Virus- or poly(I:C)-induced type I IFNs are encoded by genes targeted by the pathway. IWS1 phosphorylation-deficient cells therefore, express reduced levels of IFNα1/IFNβ1 proteins, and exhibit enhanced sensitivity to infection by multiple cytolytic viruses. Enhanced sensitivity of IWS1-deficient cells to Vesicular Stomatitis Virus and Reovirus resulted in enhanced apoptotic cell death via caspase activation. Inhibition of this pathway may therefore sensitize cancer cells to oncolytic viruses.


2018 ◽  
Vol 56 (9) ◽  
pp. 1498-1506 ◽  
Author(s):  
Clare Elizabeth Tange ◽  
Bridget Johnson-Brett ◽  
Alex Cook ◽  
Patrick Stordeur ◽  
Fabian Brohet ◽  
...  

Abstract Background: The measurement of complement components is clinically useful where a deficiency is suspected, or where excessive activation and consumption are present in disease. C2 deficiency carries an increased risk of developing systemic lupus erythematosus, recurrent infections and atherosclerosis. In this study, we have evaluated The Binding Site’s Human Complement C2 SPAPLUS® assay. Methods: Linearity was tested using 13 sample dilutions covering the standard measuring range. Within- and between-assay variabilities were calculated using five samples with different C2 concentrations. The correlation between C2 concentrations in EDTA-plasma and serum was assessed, as was the correlation between C2 measurements by the automated assay and radial immunodiffusion. C2 concentrations were compared with CH50 activity, and quantified in individuals with homozygous or heterozygous C2 deficiency, acquired angioedema and patients with chronic inflammatory conditions. Results: The assay was linear across the measuring range (3.8–42.3 mg/L). Intra- and interassay variability were 2.3%–3.8% and 0%–3.3%, respectively. Comparison between C2 measurements in EDTA-plasma and serum provided a strong correlation (p<0.0001, R2=0.82, slope 0.92), as did the correlation between the automated and radial immunodiffusion methods (p<0.0001, R2=0.89, slope 1.07). A positive correlation between C2 concentration and CH50 activity was demonstrated (p<0.0001, R2=0.48). Significant differences were observed between the median C2 concentrations obtained in healthy controls and the patient clinical samples, with homozygous C2-deficient patients giving below detectable results. Conclusions: This C2 SPAPLUS® assay allows the automated, rapid and precice quantification of complement C2 protein and could therefore be considered as a replacement for older, more time-consuming methods.


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