objective(s):previous studies demonstrate that changes in pre-mrna splicing play a significant role in human disease development. furthermore, many cancer-associated genes are regulated by alternative splicing. there are mounting evidences that splice variants which express predominantly in tumors, have clear diagnostic value and may provide potential drug targets. located on the x chromosome, ...

Western General Hospital generates different forms of the mRNA and functionally Crewe Road different proteins. This is accomplished by modulation Edinburgh EH4 2XU of the basic splicing mechanism, frequently involving changes in the relative activities of antagonistic factors. Key players are the SR protein family. These consist of Introduction one or two RNA-recognition motifs (RRMs) plus a C-...

vascular endothelial growth factor (vegf-a) is one of the most important regulatory factors in pathological and physiological angiogenesis. alternative splicing is a complicated molecular process in vegf-a gene expression which adds complexity to vegf-a biology. among all vegf-a exons, alternative splicing of exon 8 is the key determinant of isoform switching from pro-angiogenic vegf-xxx to ant...

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Most SMA cases are associated with the low levels of SMN owing to deletion of Survival Motor Neuron 1 (SMN1). SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Hence, correction of aberrant splicing of SMN2 exon 7 holds the potential for cure of SM...

Histone deacetylases (HDACs) have a central role in the regulation of gene expression. Here we investigated whether HDAC7 has an impact on embryonic stem (ES) cell differentiation into smooth muscle cells (SMCs). ES cells were seeded on collagen-IV-coated flasks and cultured in the absence of leukemia inhibitory factor in differentiation medium to induce SMC differentiation. Western blots and d...

DNA ligase I-deficient 46BR.1G1 cells show a delay in the maturation of replicative intermediates resulting in the accumulation of single- and double-stranded DNA breaks. As a consequence the ataxia telangiectasia mutated protein kinase (ATM) is constitutively phosphorylated at a basal level. Here, we use 46BR.1G1 cells as a model system to study the cell response to chronic replication-depende...

Abstract Dysregulated RNA alternative splicing (AS) is a hallmark of cancer and has been studied in cancers including glioma. However, whether the dysregulated AS regulating RNA-binding proteins (RBPs) drive gliomagenesis role glioma driver mutations shaping RBP/AS landscape have not studied. Here we describe two AS-defined subtypes that correlate with IDH1 mutation, tumor grade, patient progno...