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Exon

About: Exon is a research topic. Over the lifetime, 38308 publications have been published within this topic receiving 1745408 citations. The topic is also known as: exons.


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Journal ArticleDOI
TL;DR: The results indicate that sequences contained within the 5' and 3' ends of the c-myc transcript can affect cytoplasmic stability, and that 3' untranslated sequences of c- myc exon 3 are required for, but do not ensure, a high rate of transcript turnover in the cy toplasm.
Abstract: Expression of the c-myc gene can be controlled by transcriptional or posttranscriptional mechanisms (or both), depending on the cell type and the growth conditions. An important mechanism of posttranscriptional regulation is modulation of cytoplasmic c-myc mRNA stability; normal human and murine c-myc mRNAs have cytoplasmic half-lives of 30 min or less. To elucidate the c-myc sequences which impart this unusually high rate of cytoplasmic transcript turnover, we have constructed various deletion and hybrid c-myc genes and analyzed the cytoplasmic stability of the mRNAs produced from them in stably transfected murine fibroblasts. The results indicate that sequences contained within the 5' and 3' ends of the c-myc transcript can affect cytoplasmic stability. Specifically, the 3' untranslated sequences of c-myc exon 3 are required for, but do not ensure, a high rate of transcript turnover in the cytoplasm. Exon 2 coding sequences do not seem to be involved, and exon 1 sequences at the 5' end of the transcript have only a small effect on cytoplasmic transcript stability. The sequences that are primarily responsible for the short c-myc RNA half-life were localized to a region of 140 bases in the 3' untranslated region.

316 citations

Journal ArticleDOI
TL;DR: Results suggest that this 14 amino acid region of exon 2 of the adenovirus 2/5 E1A oncogene product, the 243R protein, may contain a function that is important for immortalization and negative modulation of tumorigenesis and metastasis.
Abstract: We have examined a series of small deletion mutants within exon 2 of the adenovirus 2/5 E1A oncogene product, the 243R protein, for immortalization, ras cooperative transformation, tumorigenesis and metastasis. Compared with wild-type 243R, various deletion mutants located between residues 193 and 243 cooperated more efficiently with ras to induce large transformed foci of less adherent cells that were tumorigenic and metastatic. However, the greatest enhancement of transformation (comparable to that obtained with a deletion of the C-terminal 67 amino acids) was observed with a mutant carrying a deletion of residues 225-238. This mutant was also more defective in immortalization. These results suggest that this 14 amino acid region may contain a function that is important for immortalization and negative modulation of tumorigenesis and metastasis. To identify cellular proteins that may associate with the exon 2-coded region of E1A (C-terminal half) and modulate its transformation potential, we constructed a chimeric gene coding for the C-terminal 68 amino acids of E1a fused to bacterial glutathione-S-transferase (GST). This fusion protein was used to purify cellular proteins that bind to the C-terminal region of E1a. A 48 kDa cellular protein doublet (designated CtBP) was found to bind specifically to the GST-E1a C-terminal fusion protein as well as to bacterially expressed full-length E1a (243R) protein. It also co-immunoprecipitated specifically with E1a. Analysis of a panel of GST-E1a C-terminal mutant proteins indicates that residues 225-238 are required for the association of E1a and CtBP, suggesting a correlation between the association of CtBP and the immortalization and transformation modulating activities of exon 2. CtBP is a phosphoprotein and the level of phosphorylation of CtBP appears to be regulated during the cell cycle, suggesting that it may play an important role during cellular proliferation.

316 citations

Journal ArticleDOI
TL;DR: Several cases of exon skipping in both normal controls and patients for whom no underlying defect could be found in genomic DNA were also observed, suggesting caution in the interpretation ofExon deletions observed in ATM cDNA when there is no accompanying identification of genomic mutations.
Abstract: Mutations resulting in defective splicing constitute a significant proportion (30/62 [48%]) of a new series of mutations in the ATM gene in patients with ataxia-telangiectasia (AT) that were detected by the protein-truncation assay followed by sequence analysis of genomic DNA. Fewer than half of the splicing mutations involved the canonical AG splice-acceptor site or GT splice-donor site. A higher percentage of mutations occurred at less stringently conserved sites, including silent mutations of the last nucleotide of exons, mutations in nucleotides other than the conserved AG and GT in the consensus splice sites, and creation of splice-acceptor or splice-donor sites in either introns or exons. These splicing mutations led to a variety of consequences, including exon skipping and, to a lesser degree, intron retention, activation of cryptic splice sites, or creation of new splice sites. In addition, 5 of 12 nonsense mutations and 1 missense mutation were associated with deletion in the cDNA of the exons in which the mutations occurred. No ATM protein was detected by western blotting in any AT cell line in which splicing mutations were identified. Several cases of exon skipping in both normal controls and patients for whom no underlying defect could be found in genomic DNA were also observed, suggesting caution in the interpretation of exon deletions observed in ATM cDNA when there is no accompanying identification of genomic mutations.

316 citations

Journal ArticleDOI
TL;DR: It is shown here that the repression of nPTB expression during myoblast differentiation results from its targeting by the muscle-restricted microRNA miR-133, which directly down-regulates a key splicing factor during muscle development and establishes a role for microRNAs in the control of a developmentally dynamic splicing program.
Abstract: Alternative pre-mRNA splicing determines many changes in gene expression during development. Two regulators known to control splicing patterns during neuron and muscle differentiation are the polypyrimidine tract-binding protein (PTB) and its neuronal homolog nPTB. These proteins repress certain exons in early myoblasts, but upon differentiation of mature myotubes PTB/nPTB expression is reduced, leading to increased inclusion of their target exons. We show here that the repression of nPTB expression during myoblast differentiation results from its targeting by the muscle-restricted microRNA miR-133. During differentiation of C2C12 myoblasts, nPTB protein but not mRNA expression is strongly reduced, concurrent with the up-regulation of miR-133 and the induction of splicing for several PTB-repressed exons. Introduction of synthetic miR-133 into undifferentiated C2C12 cells leads to a decrease in endogenous nPTB expression. Both the miR-133 and the coexpressed miR-1/206 microRNAs are extremely conserved across animal species, and PTB proteins are predicted targets for these miRNAs in Drosophila, mice, and humans. There are two potential miR-133-responsive elements (MRE) within the nPTB 3' untranslated region (UTR), and a luciferase reporter carrying this 3' UTR is repressed by miR-133 in an MRE-dependent manner. Transfection of locked nucleic acid (LNA) oligonucleotides designed to block the function of miR-133 and miR-1/206 increases expression of nPTB and decreases the inclusion of PTB dependent exons. These results indicate that miR-133 directly down-regulates a key splicing factor during muscle development and establishes a role for microRNAs in the control of a developmentally dynamic splicing program.

316 citations

Journal ArticleDOI
TL;DR: In this paper, the molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human androgen receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon.
Abstract: The molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human androgen receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon. An inverse relationship was observed between CAG repeat length and AR mRNA and protein levels. Trinucleotide repeat lengths of 43 and 65 associated with spinal/bulbar muscular atrophy decreased AR mRNA and protein levels but did not alter equilibrium binding affinity for [3H]R1881 or inherent transcriptional activity of AR, expressed as androgen-dependent fold induction of a mouse mammary tumor virus promoter-luciferase reporter vector. The findings indicate that glutamine expansion up to 66 residues in the NH2-terminal domain of AR does not alter AR functional activity. Rather, CAG repeat expansion in the region of the first exon reduces AR mRNA and protein expression. The study reveals a previously unrecognized effect of CAG repeat length on AR mRNA expression and a novel molecular mechanism for androgen resistance.

315 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20231,618
20222,004
2021905
2020908
2019887
2018909