Analysis of the Impact of Known SPINK1 Missense Variants on Pre-mRNA Splicing and/or mRNA Stability in a Full-Length Gene Assay
نویسندگان
چکیده
It is increasingly appreciated that missense variants may not only alter protein structure and function but may also influence pre-mRNA splicing and/or mRNA stability. Here we explore this issue in the context of currently known SPINK1 missense variants using a full-length gene assay. We demonstrated that 4 (17%) out of 24 variants tested significantly reduced pre-mRNA splicing and/or stability as compared with the wild-type. However, since the strongest effect observed was a 23% reduction from normal, the contribution of SPINK1 missense variants to the clinical phenotype through an impact on mRNA processing alone may be relatively minor compared with their effects in relation to protein structure/function.
منابع مشابه
In vitro and in silico evidence against a significant effect of the SPINK1 c.194G>A variant on pre-mRNA splicing.
We read with interest the recent publication of Beer and Sahin-Tóth reporting that exonic variants affecting pre-mRNA splicing contribute to the genetic burden in chronic pancreatitis. One particular variant, affecting the last nucleotide of exon 3 of the SPINK1 gene, c.194G>A, was found to cause an ∼80% reduction in SPINK1 mRNA expression as compared with the wild type in a minigene assay perf...
متن کاملColony Forming Unit Endothelial Cells Do not Exhibit Telomerase Alternative Splicing Variants and Activity
Introduction: Endothelial progenitor colony forming unit-endothelial cells (CFU-EC) were first believed to be the progenitors of endothelial cells, named endothelial progenitor cells. Further studies revealed that they are monocytes regulating vasculogenesis. The main hindrance of these cells for therapeutic purposes is their low frequency and limited replicative potentials. This study was unde...
متن کاملIs the SPINK1 p.Asn34Ser Missense Mutation Per se the True Culprit within its Associated Haplotype?
Although SPINK1, which encodes the pancreatic secretory trypsin inhibitor (PSTI), has been firmly established as a chronic pancreatitis-predisposing gene, the causal variant within the most common c.101A>G (p.Asn34Ser)-containing haplotype remains to be identified. The low penetrance of this haplotype implies a minor effect on gene expression and/or protein function; such a minor effect may not...
متن کاملComputational approach towards identification of pathogenic missense mutations in AMELX gene and their possible association with amelogenesis imperfecta
Amelogenin gene (AMEL-X) encodes an enamel protein called amelogenin, which plays a vital role in tooth development. Any mutations in this gene or the associated pathway lead to developmental abnormalities of the tooth. The present study aims to analyze functional missense mutations in AMEL-X genes and derive an association with amelogenesis imperfecta. The information on miss...
متن کاملBacterial Expression and Functional Characterization of A Naturally Occurring Exon6-less Preprochymosin cDNA
Chymosin (Rennin EC 3.4.23.4), an aspartyl proteinase, is the major proteolytic enzyme in the fourthstomach of the unweaned calf, and it is formed by proteolytic activation of its zymogene, prochymosin.Following the cloning of synthesized cDNAs on mRNA pools extracted from the mucosa of the calf fourthstomach, we have identified an alternatively spliced form of preprochymosin ...
متن کامل