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mRNA Isoforms (mrna + isoform)
Selected AbstractsRNA editing and alternative splicing of human serotonin 2C receptor in schizophreniaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003Stella Dracheva Abstract Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT2CRs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was ,,50% of that observed for the full-length isoform. [source] RCAN1-1L is overexpressed in neurons of Alzheimer's disease patientsFEBS JOURNAL, Issue 7 2007Cathryn D. Harris At least two different isoforms of RCAN1 mRNA are expressed in neuronal cells in normal human brain. Although RCAN1 mRNA is elevated in brain regions affected by Alzheimer's disease, it is not known whether the disease affects neuronal RCAN1, or if other cell types (e.g. astrocytes or microglia) are affected. It is also unknown how many protein isoforms are expressed in human brain and whether RCAN1 protein is overexpressed in Alzheimer's disease. We explored the expression of both RCAN1-1 and RCAN1-4 mRNA isoforms in various cell types in normal and Alzheimer's disease postmortem samples, using the combined technique of immunohistochemistry and in situ hybridization. We found that both exon 1 and exon 4 are predominantly expressed in neuronal cells, and no significant expression of either of the exons was observed in astocytes or microglial cells. This was true in both normal and Alzheimer's disease brain sections. We also demonstrate that RCAN1-1 mRNA levels are approximately two-fold higher in neurons from Alzheimer's disease patients versus non-Alzheimer's disease controls. Using western blotting, we now show that there are three RCAN1 protein isoforms expressed in human brain: RCAN1-1L, RCAN1-1S, and RCAN1-4. We have determined that RCAN1-1L is expressed at twice the level of RCAN1-4, and that there is very minor expression of RCAN1-1S. We also found that the RCAN1-1L protein is overexpressed in Alzheimer's disease patients, whereas RCAN1-4 is not. From these results, we conclude that RCAN1-1 may play a role in Alzheimer's disease, whereas RCAN1-4 may serve another purpose. [source] Aberrant splicing of the PTPRD gene mimics microdeletions identified at this locus in neuroblastomasGENES, CHROMOSOMES AND CANCER, Issue 3 2008Prakash Nair Neuroblastoma (NBL), a pediatric tumor arising from precursor cells of the sympathetic nervous system, is characterized by numerous recurrent large-scale chromosomal imbalances. High resolution oligonucleotide array CGH analysis of NBL has previously identified microdeletions that are confined to the 5, UTR of the protein tyrosine phosphatase receptor D (PTPRD) gene, implicating this gene in the pathogenesis of these tumors. Here, we demonstrate that the 5, UTR of this gene, consisting of 11 noncoding exons, is also aberrantly spliced in >50% of NBL primary tumors and cell lines. The loss of exons from the 5, UTR region through aberrant splicing results in aberrant mRNA isoforms that are similar to those generated through microdeletions. The aberrant splicing or microdeletion of 5, UTR exons in such a high proportion of tumors indicates that loss of these exons dys-regulates the mRNA sequence. To further validate the role of PTPRD in NBL, we have examined the expression of this gene in normal fetal adrenal neuroblasts (the cell of origin of NBL) and in tumors from patients with either low stage or high stage disease. This gene is expressed at lower levels in high stage NBL tumors, particularly those with amplification of MYCN, relative to low stage tumors or normal fetal adrenal neuroblasts, consistent with the possibility that loss of the 5, UTR exons have destabilized the mRNA. © 2007 Wiley-Liss, Inc. [source] Spatiotemporal Localization of VEGF-A Isoforms in the Mouse Postnatal Growth PlateTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2008Kristin D. Evans Abstract Vascular endothelial growth factor (VEGF) is implicated as a key angiogenic factor in the development of endochondral long bone. Several studies have evaluated the role of VEGF in prenatal endochondral bone development, but few have evaluated VEGF postnatally. Growth plates from mice at postnatal ages 14 (P14), 35 (P35), 49 (P49), and 77 (P77) days were examined for differential expression of the primary VEGF-A mRNA isoforms: VEGF 120, VEGF 164, and VEGF 188. VEGF 120 isoform expression was stable across all ages, whereas VEGF 164 had significantly less expression at P35 and P49 and VEGF l88 expression increased with increasing age. The proportion of transcript isoforms expressed at a given age also changed with VEGF 120 being expressed more highly at P35 and P49 than the other two isoforms. Changes in VEGF mRNA isoforms across cell types within the growth plate were assessed by Percoll fractionation of growth plate cells at age P28. Cells of the proliferative and early hypertrophic regions had significantly higher total VEGF mRNA expression relative to the resting and late hypertrophic regions. VEGF protein expression assessed by immunohistochemistry showed variable expression patterns with increasing postnatal age. In contrast, FLK-1 (VEGF Receptor-2) expression was restricted to the hypertrophic region. These results indicate that VEGF continues to play a significant role in endochondral bone development throughout the entire growth phase of postnatal bone development. Anat Rec, 291:6,13, 2007. © 2007 Wiley-Liss, Inc. [source] | ||||||||||