Home About us Contact
|
Home About us Contact | ||
|
|
||
mRNA Processing (mrna + processing)
Selected AbstractsGenome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: Insights into distinctive pathogenesisINFLAMMATORY BOWEL DISEASES, Issue 7 2007Feng Wu PhD Abstract Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. Methods: To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples. Results: Unsupervised classification of a total of 36 samples yielded promising separation between the affected IBD, unaffected IBD, non-IBD colitis, and normal control samples, suggesting each sample type had a distinctive gene expression pattern. Genes differentially expressed in the CD samples compared to in the controls were related to IFN,-inducible TH1 processes (IFITM1, IFITM3, STAT1, and STAT3) and antigen presentation (TAP1, PSME2, PSMB8). The most noticeable change in the UC samples was reduced expression of genes regulating biosynthesis, metabolism, and electrolyte transport (HNF4G, KLF5, AQP8, ATP2B1, and SLC16A). Twenty-five percent of genes down-regulated in the UC samples were also down-regulated in the infectious colitis samples. Unaffected biopsy samples of IBD patients also registered differences expression of genes compared to in the normal controls. Of these differentially expressed genes, only 2 were up-regulated, PSKH1, a regulator of mRNA processing, and PPID, a suppressor of apoptosis. Conclusions: The study shows that the gene expression patterns of IBD, CD in particular, are quite different from those of infectious colitis, highlighting distinctive expression of genes and pathways in UC and CD. (Inflamm Bowel Dis 2007) [source] Elevated plasma fibrinogen ,, concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factorsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007M. N. MANNILA Summary., Background:, Fibrinogen ,,, a fibrinogen ,-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. Objective:, The present case,control study searched for potential determinants of the plasma fibrinogen ,, concentration and examined the relationship between this variant and risk of myocardial infarction (MI). Patients and methods:, The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen ,, concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. Results:, The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen ,, concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen ,, concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen ,, concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. Conclusions:, Plasma fibrinogen ,, concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles. [source] The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNAMOLECULAR CARCINOGENESIS, Issue 3 2010Leslie J. Farber Abstract Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in sporadic parathyroid and renal tumors. However, the mechanisms by which parafibromin suppresses tumor formation remain unknown. In this study, we identify a novel role of parafibromin in the regulation of replication-dependent histones. Both in vitro and in vivo analyses reveal a posttranscriptional role of parafibromin in histone mRNA processing. Downregulation of parafibromin through RNA interference or in vivo mutations lead to uncleaved histone mRNA with polyadenylated tails. These results indicate that parafibromin regulates the 3, processing of histone RNA, an essential component of the cell cycle. © 2009 Wiley-Liss, Inc. [source] High-resolution Melting Facilitates Mutation Screening of PYGM in Patients with McArdle DiseaseANNALS OF HUMAN GENETICS, Issue 3 2009Morten Duno Summary Mutations in PYGM, encoding the muscle-specific glycogen phosphorylase (myophosphorylase), are responsible for McArdle disease. Among Caucasians, a large proportion of patients are homozygous for the R50X mutation, but other mutations can affect all the 20 exons of PYGM, making mutation detection laborious. We have developed a high-resolution melting (HRM) assay for mutation detection in PYGM. Twelve McArdle patients were investigated, in whom pre-screening had ruled out homozygosity or compound heterozygosity for the two common G205S and R50X mutations. In total, we identified 16 different variations. Thirteen of these are pathogenic, and three were classified as polymorphisms. Nine variations had not previously been described. One of the novel mutations, c.2430C > T, was initially predicted to result in a silent G810G change, but cDNA analysis demonstrated that the mutation led to abnormal mRNA processing. The HRM protocol reduced the need for direct sequencing by approximately 85%, and is a good approach to search for new mutations in PYGM. [source] Crystallization and preliminary crystallographic analysis of eukaryotic transcription and mRNA export factor Iws1 from Encephalitozoon cuniculiACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2010Michael Koch Transcription elongation by eukaryotic RNA polymerase II requires the coupling of mRNA synthesis and mRNA processing and export. The essential protein Iws1 is at the interface of these processes through its interaction with histone chaperone and elongation factor Spt6 as well as with complexes involved in mRNA processing and export. Upon crystallization of the evolutionarily conserved domain of Iws1 from Encephalitozoon cuniculi, four different crystal forms were obtained. Three of the crystal forms belonged to space group P21 and one belonged to space group P2221. Preliminary X-ray crystallographic analysis of one of the crystal forms allowed the collection of data to 2.5,Å resolution. [source] | ||||||||||