SEARCH · PubMed Health

Results for “Exons”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed1992

Molecular cloning and exon-intron mapping of the gene encoding human transmembrane secretory component (the poly-Ig receptor)

Secretory component (SC or the poly-Ig receptor) plays a crucial role in mucosal immunity by translocating polymeric IgA and IgM through secretory epithelial cells into external body fluids. Labeled restriction fragments from human SC cDNA were used to screen a human genomic leukocyte library. Three overlapping clones, spanning a total of 19 kb of the human SC gene, including 3 kb of the 5' flanking region, were characterized. The putative TATA box candidate, preceded by a CAAT-like box, was found 329 nucleotides upstream of the first exon. Altogether 11 exons covering the entire coding region were identified. The exon size ranged from 59 to 657 nucleotides and exon-intron junctions followed known consensus sequences. Three of the five extracellular Ig-related domains (D1, D4 and D5) were confined to one exon each (E3, E5 and E6), whereas D2 and D3 were encoded by the same exon (E4). The latter exon corresponds to that involved in alternate splicing of rabbit SC. The membrane-spanning segment was confined to part of one exon (E8). The cytoplasmic tail was encoded by four exons (E8-E11), whose boundaries encompassed fairly well the structural determinants proposed to be responsible for intracellular sorting of SC in the rabbit. The polymorphic restriction site reported earlier for Pvu II was localized to the third intron.

Amino Acid Sequence↗

PubMed1993

In primary human breast carcinomas mutations in exons 5 and 6 of the p53 gene are associated with a high S-phase index.

A series of 121 human breast tumors was screened for point mutations in exons 5 through 8 of the p53 gene, by SSCP analysis. On the same tumor samples, the S-phase index (SPI) was determined by the incorporation of BUdR in fresh tissue. p53 mutations were observed in 29% of the cases. The frequency of point mutations for the individual exons was: exon 5, 10.0%; exon 6, 9.9%; exon 7, 7.1% and exon 8, 5.5%. Two mutations detected by SSCP were confirmed by sequencing the p53 cDNA. The presence of a p53 mutation, irrespective of its location, correlates (p = 0.003) with a high SPI. This association appears to primarily reflect mutations in exon 5 (p = 0.0002) and exon 6 (p = 0.05), since mutations in exons 7 and 8 failed to show any association. These results indicate that mutations in the p53 gene identify highly proliferating tumors, and that the position of the p53 mutation may have different effects upon the proliferative activity of tumor cells in vivo.

Base Sequence↗

PubMed1991

Muscle-specific accumulation of Drosophila myosin heavy chains: a splicing mutation in an alternative exon results in an isoform substitution.

We show that the molecular lesions in two homozygousviable mutants of the Drosophila muscle myosin heavy chain gene affect an alternative exon (exon 9a) which encodes a portion of the myosin head that is highly conserved among both cytoplasmic and muscle myosins of all organisms. In situ hybridization and Northern blotting analysis in wild-type organisms indicates that exon 9a is used in indirect flight muscles whereas both exons 9a and 9b are utilized in jump muscles. Alternative exons 9b and 9c are used in other larval and adult muscles. One of the mutations in exon 9a is a nonsense allele that greatly reduces myosin RNA stability. It prevents thick filament accumulation in indirect flight muscles and severely reduces the number of thick filaments in a subset of cells of the jump muscles. The second mutation affects the 5' splice site of exon 9a. This results in production of an aberrantly spliced transcript in indirect flight muscles, which prevents thick filament accumulation. Jump muscles of this mutant substitute exon 9b for exon 9a and consequently have normal levels of thick filaments in this muscle type. This isoform substitution does not obviously affect the ultrastructure or function of the jump muscle. Analysis of this mutant illustrates that indirect flight muscles and jump muscles utilize different mechanisms for alternative RNA splicing.

Amino Acid Sequence↗

PubMed1998

Identification of two novel 5' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts.

Previously, the comparison of human MNB/DYRK cDNA sequences with publicly available genomic DNA sequence made a conclusion that MNB/DYRK gene consists of 11 exons spanning 100 kb. Here we found a novel human MNB/DYRK cDNA clone that has the 5' end different from any of those reported MNB/DYRK cDNAs. The 5' end of this cDNA resides in a CpG island associated with the NotI linking clone LL390 that is located more than 50 kb upstream of the exon that contains an initiation codon ATG. Northern blot analysis indicated that almost all the MNB/DYRK transcripts start from the newly identified 5'-noncoding exon. PCR amplification of cDNAs from various human tissues indicated that some mRNAs contain an additional noncoding exon of 76 bp next to the 5'-end exon and there are at least three types of MNB/DYRK mRNAs containing alternatively spliced 5' exons including two novel exons. We now conclude that human MNB/DYRK gene consists of 13 exons (not 11 exons) spanning about 150 kb (not 100 kb).

Alternative Splicing↗

PubMed1998

Identification of various exon-deleted progesterone receptor mRNAs in human endometrium and ovarian endometriosis.

We demonstrated the expression of various exon-deleted progesterone receptor (PR) variant mRNAs in human uterine endometrium and ovarian endometriosis using the reverse transcription-polymerase chain reaction-DNA sequencing analyses. In addition to PR wild-type mRNA, various exon-deleted PR variant mRNAs were identified in all samples analyzed. The sequence of these variants showed a perfect junction between exons surrouding the deletion area. PR wild-type, exon 6-deleted, exon 4-deleted, exon 5, 6-deleted and exon 4, 5, 6-deleted PR variant mRNAs were observed in all samples analyzed. Exon 4, 6-deleted PR mRNA was observed only in ovarian endometriosis. This is the first study to demonstrate the coexpression of various PR exon-deleted variant mRNAs with the wild-type in uterine endometrium and ovarian endometriosis. All resulting variant proteins might indicate functional diversity and modify the progestational action of wild-type PR, and thus be involved in the pathophysiology of ovarian endometriosis.

Adult↗

PubMed2000

Identification of novel first exons in Ad4BP/SF-1 (NR5A1) gene and their tissue- and species-specific usage.

It has been demonstrated that the mammalian Ad4BP/SF-1 (NR5A1) gene is regulated precisely in sex, tissue, and developmental stage specific manners. To clarify the complex transcriptional regulation, we investigated in the present study whether the gene transcription is regulated by multiple promoters accompanied by noncoding first exons. Novel first exons (Io and Ig) were identified downstream of the already identified exon Ia. Nucleotide sequences revealed that Ia and Ig exons were well conserved, whereas Io exon was less conserved among the mouse, rat, and human genes. Interestingly, the splice donor of the mouse and human Io and human Ig exons do not satisfy the consensus sequence. Transcripts containing Ia, Io, and Ig were detected in all rat tissues examined, while the transcript containing Io was undetectable in the corresponding tissues of mice. The lack of exon Io usage in the mouse was confirmed by transient transfection assays with cultured cells. Quantitative RT-PCR analysis revealed that the transcript containing Ig exon was the main product in the pituitary but significantly less in the spleen, suggesting that the regulation of Ad4BP/SF-1 gene transcription in the pituitary and spleen is distinct from that of other tissues. The above findings, together with the structural abnormality at the splice donor site, suggest that acquisition of the multiple first exons enables the Ad4BP/SF-1 gene to be regulated differentially in different animal species and in different tissues in the same animal.

Alternative Splicing↗

PubMed2002

Additional 5' exons in the RGS3 locus generate multiple mRNA transcripts, one of which accounts for the origin of human PDZ-RGS3.

Regulators of G-protein signaling (RGS) proteins can be broadly divided into those that consist predominantly of an RGS domain and those that possess an RGS domain along with additional domains. RGS3 fits into both categories, as both short and longer forms exist. Recently, a novel form of mouse RGS3 that possesses a PDZ domain was identified. Here we show that the human PDZ-RGS3 isoform arises from 10 upstream exons along with 6 exons from the previously characterized RGS3. We found that 47,000 nucleotides span the last of the 10 upstream exons and the first exon used from the original cluster of RGS3 exons. These 10 upstream exons encode 398 amino acids, which show strong conservation with those from mouse PDZ-RGS3. In addition, another isoform exists that uses 17 upstream exons, 9 of which overlap with those in PDZ-RGS3, along with the same 6 downstream exons used in PDZ-RGS3. Finally, a short form of human RGS3 arises from an unrecognized RGS3 exon that encodes an amino-terminal 140 amino acids. For each RGS3 isoform, RT-PCR detected specific mRNA transcripts and immunoblot analysis identified specific bands for RGS3 and PDZ-RGS3. RGS3 provides an example of the complex origins of the coding regions of mammalian proteins.

Alternative Splicing↗

PubMed1990

Evolution of collagen IV genes from a 54-base pair exon: a role for introns in gene evolution.

The exon structure of the collagen IV gene provides a striking example for collagen evolution and the role of introns in gene evolution. Collagen IV, a major component of basement membranes, differs from the fibrillar collagens in that it contains numerous interruptions in the triple helical Gly-X-Y repeat domain. We have characterized all 47 exons in the mouse alpha 2(IV) collagen gene and find two 36-, two 45-, and one 54-bp exons as well as one 99- and three 108-bp exons encoding the Gly-X-Y repeat sequence. All these exons sizes are also found in the fibrillar collagen genes. Strikingly, of the 24 interruption sequences present in the alpha 2-chain of mouse collagen IV, 11 are encoded at the exon/intron borders of the gene, part of one interruption sequence is encoded by an exon of its own, and the remaining interruptions are encoded within the body of exons. In such "fusion exons" the Gly-X-Y encoding domain is also derived from 36-, 45-, or 54-bp sequence elements. These data support the idea that collagen IV genes evolved from a primordial 54-bp coding unit. We furthermore interpret these data to suggest that the interruption sequences in collagen IV may have evolved from introns, presumably by inactivation of splice site signals, following which intronic sequences could have been recruited into exons. We speculated that this mechanism could provide a role for introns in gene evolution in general.

Amino Acid Sequence↗

PubMed2004

Exon deletions of parkin gene in patients with Parkinson disease.

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.

Adult↗

PubMed2005

Deletion and mutation of WWOX exons 6-8 in human non-small cell lung cancer.

To examine the deletion and point mutation of WWOX (WW domain containing oxidoreductase) exons 6-8 in human non-small cell lung cancer and their possible relationship with pathological stages, tumor tissues and the corresponding normal tissues were obtained from 44 Chinese patients who had undergone surgery for non-small cell lung cancer. RNA was extracted from each sample and deletion and mutation of WWOX exons 6-8 were analyzed by RT-PCR and DNA sequencing. Our results showed that 28 of 44 (63.6%) lung cancer samples showed loss of WWOX exons 6-8 transcript and the deletion was detected in only 3 of 44 (6.8%) corresponding adjacent normal tissues (P < 0.05). The transcript sequencing analyses of the 16 lung cancer samples without transcript loss of WWOX exons 6-8 revealed no difference from the sequence of GenBank. Moreover, the deletion of WWOX exons 6-8 was significantly higher in the smokers when compared with the non-smokers. It is also higher in the men and squamous carcinomas than in women and adenocarcinomas (P < 0. 05). The deletion, however, was not found to be associated with pathological stages of the tumors. Our study documented a high incidence of deletion of WWOX exons 6-8 in non-small cell lung cancer in Chinese patients and suggested that the frequent loss of WWOX exons 6-8 might play an important role in the tumorigenesis of non-small cell lung cancer in Chinese. WWOX exons 6-8 may serves as a candidate molecular target of smoking carcinogenesis, and point mutation is not a predominant way of alteration of WWOX exons 6-8.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Expression of estrogen receptor alpha exon 5 and 7 deletion variant in human breast cancers.

BACKGROUND: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function. METHODS: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases. CONCLUSIONS: We suspect that the exon 5 deletion does not work as a dominant positive.

Breast↗

PubMed1997

Comparative evolutionary rates of introns and exons in murine rodents.

Analysis of DNA sequences of 132 introns and 140 exons from 42 pairs of orthologous genes of mouse and rat was used to compare patterns of evolutionary change between introns and exons. The mean of the absolute difference in length (measured in base pairs) between the two species was nearly five times as high in the case of introns as in the case of exons. The average rate of nucleotide substitution in introns was very similar to the rate of synonymous substitution in exons, and both were about three times the rate of substitution at nonsynonymous sites in exons. G+C content of introns and exons of the same gene were correlated; but mean G+C content at the third positions of exons was significantly higher than that of introns or positions 1-2 of exons from the same gene. G+C content was conserved over evolutionary time, as indicated by strong correlations between mouse and rat; but the change in G+C content was greatest at position 3 of exons, intermediate in introns, and lowest at positions 1-2 in introns.

Animals↗

PubMed2006

The mutually exclusive flip and flop exons of AMPA receptor genes were derived from an intragenic duplication in the vertebrate lineage.

The incomplete correlation between the organismal complexities and the number of genes among eukaryotic organisms can be partially explained by multiple protein products of a gene created by alternative splicing. One type of alternative splicing involves alternative selection of mutually exclusive exons and creates protein products with substitution of one segment of the amino acid sequence for another. To elucidate the evolution of the mutually exclusive 115-bp exons, designated flip and flop, of vertebrate AMPA receptor genes, the gene structures of chordate (tunicate, cephalochordate, and vertebrate) and protostome (Drosophila and Caenorhabditis elegans) AMPA receptor subunits were compared. Phylogenetic analysis supports that the vertebrate flip and flop exons evolved from a common sequence. Flip and flop exons exist in all vertebrate AMPA receptor genes but only one 115-bp exon is present in the genes of tunicates and cephalochordates, suggesting that the exon duplication event occurred at the ancestral vertebrate AMPA receptor gene after the separation of vertebrates from primitive chordates. The structures of animal AMPA receptor genes also suggest that an intron insertion to separate the primordial flip/flop exon from the M4-coding exon occurred before the exon duplication event and probably at the chordate lineage.

Alternative Splicing↗

PubMed2004

An intragenic deletion/inversion event in the DMD gene determines a novel exon creation and results in a BMD phenotype.

Duchenne and Becker Muscular Dystrophy (DMD and BMD) are caused, in the majority of cases, by deletions in the dystrophin gene ( DMD). Here we describe the unprecedented case of a BMD patient carrying a large out-of-frame intragenic deletion, together with an inversion in the DMD gene, resulting in the inclusion of a novel exon in the transcript. Multiplex PCR amplification revealed the presence of a 48-52 exon deletion, but transcript analysis identified two unexpected products, neither of them including exon 53. The shorter mRNA derived from the juxtaposition of exons 47-54 (in-frame), while the longer one resulted from the inclusion of a novel 73-bp exon between exons 47 and 54. Sequence analysis revealed that the inserted sequence derived from an inverted portion of intron 53; its inclusion is predicted to determine protein truncation. The presence of a genomic inversion involving exon 53 and flanking regions was confirmed, and inversion/deletion breakpoints were sequenced. The inverted 73-bp sequence displays splicing signals at both ends and thus it is probably recognized as a novel exon when the partially inverted hnRNA is processed. These findings highlight the importance of mRNA analysis on patients that, based on routine DNA screenings, do not follow the reading-frame rule. This is the first reported patient carrying both an intragenic deletion and inversion in the DMD locus. This case might provide further insight into both the mechanisms that determine genomic rearrangements in the DMD locus and the molecular signals that drive exon inclusion.

Adult↗

PubMed2000

The survival motor neuron (SMN) protein: effect of exon loss and mutation on protein localization.

Spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of the survival motor neuron gene (SMN1) but not mutations in the centromeric copy (SMN2). The critical difference between the two genes is a nucleotide difference in exon 7 that affects splicing and causes this exon to be spliced out of most SMN2 transcripts. A majority of the SMN1 gene transcripts contain exon 7. To investigate the effect of exon loss or mutations in SMN on protein localization, 15 SMN constructs were prepared and transfected into COS-7 cells and fibroblasts derived from a type I SMA patient. Loss of exon 5 (Iso5-SMN), a putative nuclear localization signal in exon 2, and the G279V point mutation had little effect on SMN localization. Loss of both exons 5 and 7 (Iso57-SMN) resulted in low gem numbers and the localization of the majority of the SMN protein to the cytoplasm. Cells expressing constructs lacking only exon 7 (Iso7-SMN) did not produce large numbers of gems in general, although there were a few cells that had a staining pattern similar to cells transfected with a full-length (Full-SMN) construct. HeLa cells stably transfected with full-length SMN or Iso7-SMN did not overexpress SMN, and both constructs produced a similar localization of the protein, although Iso7-SMN formed gems less efficiently. Removal of the amino-terminus, deletion of the conserved domain in exon 2A, and the mutation Y272C all caused accumulation of SMN in the nucleus, sometimes in large aggregates. These findings suggest that the amino-terminal domain of SMN is essential for the correct cellular distribution of SMN, whereas Iso7-SMN is capable of forming gems, albeit at a reduced efficiency.

Animals↗

PubMed1994

Experimental allergic encephalomyelitis induced by the peptide encoded by exon 2 of the MBP gene, a peptide implicated in remyelination.

The discovery of T lymphocytes reactive to the peptide encoded by exon 2 of the myelin basic protein (MBP) gene in multiple sclerosis (MS) patients has drawn attention to MBP isoforms harboring that peptide as candidate autoantigens. Previously, immunological studies in MS had almost exclusively used the more abundant 18.5 kDa isoform of MBP, which does not contain the exon 2 peptide. Investigations of experimental allergic encephalomyelitis (EAE) have also focussed on the 18.5 kDa MBP isoform and its peptides. Since EAE is an animal model widely used to study MS, we examined the encephalitogenic potential of exon 2 peptide in the SJL/J mouse. Evidence for increased expression of exon 2-containing isoforms during remyelination in mouse CNS suggested that exon 2-sensitized T cells, with encephalitogenic capacity, might be important in the perpetuation of relapsing EAE (rEAE). Our experiments have demonstrated that exon 2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by the adoptive transfer of exon 2-sensitized lymphocytes. Furthermore, the disease could be accentuated by the transfer of short-term exon 2-reactive lines or by a combination of adoptive transfer and antigenic challenge with exon 2 peptide. The immunodominant epitope(s) appeared to localize to the segment bordered by amino acids 59-85.

Amino Acid Sequence↗

PubMed1995

The human high mobility group (HMG)-box transcription factor TCF-1: novel isoforms due to alternative splicing and usage of a new exon IXA.

The C-terminal peptide sequences of the human lymphocyte-specific high mobility group (HMG)-box transcription factor TCF-1 are determined by alternative splice mechanisms affecting the exons VIII to X. Here we report, in addition to four splice forms described previously (TCF-1A, B, C, D), the identification of three novel transcripts designated TCF-1E, F, G. Cloning and sequencing of the novel cDNAs revealed (i) joining of the exons VIII and IX to an internal exon X splice acceptor site resulting in a new open reading frame (ORF) of 99 amino acids derived from exon X sequences, (ii) the identification of an additional functional splice acceptor site within exon X, and (iii) a new 81-nucleotide insertion between exon VIII and exon X sequences in a novel transcript form. Genomic cloning and sequence analysis of this transcribed segment of 81 basepairs revealed that it was bordered by canonical splice consensus sites and located in a distance of some 400 bp from both the exons IX and X. It was therefore termed exon IXA. Novel ORFs were generated as a consequence of these alternative splice mechanisms resulting in TCF-1 gene products with significantly different C-terminal peptide sequences, which are prone to selective protein-protein interactions or transactivating functions.

Alternative Splicing↗

PubMed1995

Characterization of three separated exons in the HLA class II DR region of the human major histocompatibility complex.

The human major histocompatibility complex, HLA, is a highly polymorphic gene region which includes the DRA and DRB genes. The number of DRB genes differs between haplotypes. The DR4 haplotype seems to be one of the most complex with five DRB loci, DRB1, DRB4, DRB7, DRB8, and DRB9, in addition to the single DRA locus. We determined the nucleotide sequences of three separated DRB exons located between the DRB4 locus and the DRA locus in the DR4 haplotype, two DRB signal-peptide exons (S1 and S3) and one DRB first-domain exon (locus designation DRB9). Sequence comparisons suggest the following order of events for the origin of these exons: DRB9 seems to be the oldest exon and has previously been detected in multiple HLA haplotypes. DRB9 is more divergent than the three other known DRB pseudogenes, all of which have been found in apes. This suggests that DRB9 arose prior to the hominoid divergence. An L1 repeat has been inserted 3' to DRB9. Subsequently, a LTR of the ERV9 retrovirus-like family was inserted into the L1 repeat. Such LTRs have recently been observed in some of the other DRB genes. The pseudogenes DRB7 and DRB8 (containing only exons 3-6) arose after DRB9. Finally, the separated signal peptide exons S1 and S3 were formed. The molecular characterization of these separated DRB exons and insertion elements further clarifies the complex evolutionary history of the HLA-DR region. These selectively neutral exons may serve as useful markers for tracing the phylogeny of HLA haplotypes.

Base Sequence↗