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 451 records · Page 25Linked to original sources

PubMed1998

Splicing of two internal and four carboxyl-terminal alternative exons in nonmuscle tropomyosin 5 pre-mRNA is independently regulated during development.

Four nonmuscle tropomyosin isoforms have been reported to be produced from the rat Tm5 gene by alternative splicing (Beisel, K. W., and Kennedy, J. E. (1994) Gene (Amst.) 145, 251-256). In order to detect additional isoforms that might be expressed from that gene, we used reverse transcriptase-polymerase chain reaction assays and evaluated the presence of all product combinations of two alternative internal exons (6a and 6b) and four carboxyl-terminal exons (9a, 9b, 9c, and 9d) in developing and adult rat brain. We identified five different combinations for exon 9 (9a + 9b, 9a + 9c, 9a + 9d, 9c, and 9d), and the exon combinations 9a + 9c and 9a + 9d were previously unreported. Each of these combinations existed with both exon 6a and exon 6b. Thus, the rat brain generates at least 10 different isoforms from the Tm5 gene. Northern blot hybridization with alternative exon-specific probes revealed that these isoforms were also expressed in a number of different adult rat tissues, although some exons are preferentially expressed in particular tissues. Studies of regulation of the 10 different Tm5 isoform mRNAs during rat brain development indicated that no two isoforms are coordinately accumulated. Furthermore, there is a developmental switch in the use of exon 6a to exon 6b from embryonic to adult isoforms. TM5 protein isoforms show a differential localization in the adult cerebellum.

Alternative Splicing↗

PubMed2003

An in vivo replication-important function in the second coding exon of Tat is constrained against mutation despite cytotoxic T lymphocyte selection.

Human and simian immunodeficiency virus (HIV/SIV) Tat proteins are specified by two coding exons. Tat functions in the transcription of primate lentiviruses. A plethora of in vitro data currently suggests that the second coding exon of Tat is largely devoid of function. However, whether the second exon of Tat contributes functionally to viral pathogenesis in vivo remains unknown. To address this question directly, we compared infection of rhesus macaques with an SIV, engineered to express only the first coding exon of Tat (SIVtat1ex), to counterpart infection with wild-type SIVmac239 virus, which expresses the full 2-exon Tat. This comparison showed that the second coding exon of Tat contributes to chronic SIV replication in vivo. Interestingly, in macaques, we observed a cytotoxic T lymphocytes (CTL) response to the second coding exon of Tat, which appears to durably control SIV replication. When SIV mutated in an attempt to escape this second Tat-exon-CTL, the resulting virus was less replicatively fit and failed to populate the host in vivo. Our study provides the first evidence that the second coding exon in Tat embodies an important function for in vivo replication. We suggest the second coding exon of Tat as an example of a functionally constrained "epitope" whose elicited CTL response cannot be escaped by virus mutation without producing a virus that replicates poorly in vivo.

Amino Acid Sequence↗

PubMed2005

Arginine/serine-rich protein interaction domain-dependent modulation of a tau exon 10 splicing enhancer: altered interactions and mechanisms for functionally antagonistic FTDP-17 mutations Delta280K AND N279K.

Tau exon 10 splicing is altered by autosomal dominant mutations that cause frontotemporal dementia with parkinsonism chromosome 17-type and by unknown mechanisms in other related neurodegenerative disorders. Identifying cis- and trans-regulators of tau exon 10 splicing is therefore crucial for understanding disease mechanisms. We previously identified several splicing enhancers and silencers within exon 10 and intron 10. Here, we show that splicing factors SF2/ASF, Tra2beta, and a 50-kDa nuclear protein bind in vitro to the polypurine enhancer at the 5' end of exon 10. Disease splicing mutations N279K and Delta280K disrupt the enhancer and alter associations with these factors. N279K targets robustly bind Tra2beta compared with the normal enhancer, which may explain why N279K enhances exon 10 splicing in vivo. In contrast, factor associations with Delta280K targets are nearly undetectable, explaining why Delta280K almost abolishes exon 10 splicing in vivo. Small interfering RNA-mediated suppression of endogenous SF2/ASF and Tra2beta significantly reduces exon 10 splicing. Exogenous SF2/ASF dramatically enhances normal exon 10 splicing and efficiently rescues the Delta280K splicing defect. Domain deletion analyses show that the C-terminal RS domains of SF2/ASF and Tra2beta are required for normal exon 10 splicing in vivo. In contrast to Tra2beta, the SF2/ASF RS domain remains essential in the presence of a strengthened enhancer or when either weak splice site is strengthened. The data suggest that SF2/ASF has both essential and regulatory roles, whereas Tra2beta has a supporting role in exon 10 splicing.

Alternative Splicing↗

PubMed2000

Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element.

In monosymptomatic forms of cystic fibrosis such as congenital bilateral absence of vas deferens, variations in the TG(m) and T(n) polymorphic repeats at the 3' end of intron 8 of the cystic fibrosis transmembrane regulator (CFTR) gene are associated with the alternative splicing of exon 9, which results in a nonfunctional CFTR protein. Using a minigene model system, we have previously shown a direct relationship between the TG(m)T(n) polymorphism and exon 9 splicing. We have now evaluated the role of splicing factors in the regulation of the alternative splicing of this exon. Serine-arginine-rich proteins and the heterogeneous nuclear ribonucleoprotein A1 induced exon skipping in the human gene but not in its mouse counterpart. The effect of these proteins on exon 9 exclusion was strictly dependent on the composition of the TG(m) and T(n) polymorphic repeats. The comparative and functional analysis of the human and mouse CFTR genes showed that a region of about 150 nucleotides, present only in the human intron 9, mediates the exon 9 splicing inhibition in association with exonic regulatory elements. This region, defined as the CFTR exon 9 intronic splicing silencer, is a target for serine-arginine-rich protein interactions. Thus, the nonevolutionary conserved CFTR exon 9 alternative splicing is modulated by the TG(m) and T(n) polymorphism at the 3' splice region, enhancer and silencer exonic elements, and the intronic splicing silencer in the proximal 5' intronic region. Tissue levels and individual variability of splicing factors would determine the penetrance of the TG(m)T(n) locus in monosymptomatic forms of cystic fibrosis.

Animals↗

PubMed1999

Redefinition of exon 7 in the COL1A1 gene of type I collagen by an intron 8 splice-donor-site mutation in a form of osteogenesis imperfecta: influence of intron splice order on outcome of splice-site mutation.

Most splice-site mutations lead to a limited array of products, including exon skipping, use of cryptic splice-acceptor or -donor sites, and intron inclusion. At the intron 8 splice-donor site of the COL1A1 gene, we identified a G+1-->A transition that resulted in the production of several splice products from the mutant allele. These included one in which the upstream exon 7 was extended by 96 nt, others in which either intron 8 or introns 7 and 8 were retained, one in which exon 8 was skipped, and one that used a cryptic donor site in exon 8. To determine the mechanism by which exon-7 redefinition might occur, we examined the order of intron removal in the region of the mutation by using intron/exon primer pairs to amplify regions of the precursor nuclear mRNA between exon 5 and exon 10. Removal of introns 5, 6, and 9 was rapid. Removal of intron 8 usually preceded removal of intron 7 in the normal gene, although, in a small proportion of copies, the order was reversed. The proportion of abnormal products suggested that exon 7 redefinition, intron 7 plus intron 8 inclusion, and exon 8 skipping all represented products of the impaired rapid pathway, whereas the intron-8 inclusion product resulted from use of the slow intron 7-first pathway. The very low-abundance cryptic exon 8 donor site product could have arisen from either pathway. These results suggest that there is commitment of the pre-mRNA to the two pathways, independent of the presence of the mutation, and that the order and rate of intron removal are important determinants of the outcome of splice-site mutations and may explain some unusual alterations.

Amino Acid Sequence↗

PubMed1993

The gene for C10, a member of the beta-chemokine family, is located on mouse chromosome 11 and contains a novel second exon not found in other chemokines.

C10 is a recently described member of the beta-chemokine subfamily of the chemokine superfamily of cytokine proteins. Genomic clones encoding murine C10 were isolated and sequenced. The other members of the beta-chemokine family have a three-exon genomic structure containing, among other sequence similarities, four cysteines spaced in a highly conserved manner. In each of these genes, the second exon contains the first three of the four conserved cysteines, and the third exon contains the last. In contrast to this genomic structure, the C10 gene has four exons, with a novel second exon of 48 nucleotides. Exons 3 and 4 of C10 contain four cysteines distributed in the same manner as in exons 2 and 3 of other beta-chemokine family members. The novel second exon codes for a large number of charged amino acids, and this exon shows no homology to any previously described sequences in computer databases. Linkage studies showed that the C10 gene (Scya6) is closely linked to the Scya2 locus on mouse chromosome 11, indicating that the C10 gene is located in the same region of mouse chromosome 11 as other members of the beta-chemokine family. Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family.

Amino Acid Sequence↗

PubMed1994

Constructing gene models from accurately predicted exons: an application of dynamic programming.

This paper presents a computationally efficient algorithm, the Gene Assembly Program III (GAP III), for constructing gene models from a set of accurately-predicted 'exons'. The input to the algorithm is a set of clusters of exon candidates, generated by a new version of the GRAIL coding region recognition system. The exon candidates of a cluster differ in their presumed edges and occasionally in their reading frames. Each exon candidate has a numerical score representing its 'probability' of being an actual exon. GAP III uses a dynamic programming algorithm to construct a gene model, complete or partial, by optimizing a predefined objective function. The optimal gene models constructed by GAP III correspond very well with the structures of genes which have been determined experimentally and reported in the Genome Sequence Database (GSDB). On a test set of 137 human and mouse DNA sequences consisting of 954 true exons, GAP III constructed 137 gene models using 892 exons, among which 859 (859/954 = 90%) are true exons and 33 (33/892 = 3%) are false positive. Among the 859 true positives, 635 (74%) match the actual exons exactly, and 838 (98%) have at least one edge correct. GAP III is computationally efficient. If we use E and C to represent the total number of exon candidates in all clusters and the number of clusters, respectively, the running time of GAP III is proportional to (E x C).

Algorithms↗

PubMed2005

Detecting tissue-specific alternative splicing and disease-associated aberrant splicing of the PTCH gene with exon junction microarrays.

Mutations in the human ortholog of Drosophila patched (PTCH) have been identified in patients with autosomal dominant nevoid basal cell carcinoma syndrome (NBCCS), characterized by minor developmental anomalies and an increased incidence of cancers such as medulloblastoma and basal cell carcinoma. We identified many isoforms of PTCH mRNA involving exons 1-5, exon 10 and a novel exon, 12b, generated by alternative splicing (AS), most of which have not been deposited in GenBank nor discussed earlier. To monitor splicing events of the PTCH gene, we designed oligonucleotide arrays on which exon probes and exon-exon junction probes as well as a couple of intron probes for the PTCH gene were placed in duplicate. Probe intensities were normalized on the basis of the total expression of PTCH and probe sensitivity. Tissue-specific regulation of AS identified with the microarrays closely correlated with the results obtained by RT-PCR. Of note, the novel exon, exon 12b, was specifically expressed in the brain and heart, especially in the cerebellum. Additionally, using these microarrays, we were able to detect disease-associated aberrant splicings of the PTCH gene in two patients with NBCCS. In both cases, cryptic splice donor sites located either in an exon or in an intron were activated because of the partial disruption of the consensus sequence for the authentic splice donor sites due to point mutations. Taken together, oligonucleotide microarrays containing exon junction probes are demonstrated to be a powerful tool to investigate tissue-specific regulation of AS and aberrant splicing taking place in genetic disorders.

Alternative Splicing↗

PubMed1993

cis-elements involved in alternative splicing in the rat beta-tropomyosin gene: the 3'-splice site of the skeletal muscle exon 7 is the major site of blockage in nonmuscle cells.

We have been using the rat beta-tropomyosin (beta-TM) gene as a model system to study the mechanism of alternative splicing. The beta-TM gene spans 10 kb with 11 exons and encodes two distinct isoforms, namely skeletal muscle beta-TM and fibroblast TM-1. Exons 1-5, 8, and 9 are common to all mRNAs expressed from this gene. Exons 6 and 11 are used in fibroblasts, as well as in smooth muscle cells, whereas exons 7 and 10 are used exclusively in skeletal muscle cells. Our previous studies localized the critical elements for regulated alternative splicing to sequences within exon 7 and the adjacent upstream intron. We also demonstrated that these sequences function, in part, to regulate splice-site selection in vivo by interacting with cellular factors that block the use of the skeletal muscle exon in nonmuscle cells (1). Here we have further characterized the critical cis-acting elements involved in alternative splice site selection. Our data demonstrate that exon 7 and its flanking intron sequences are sufficient to regulate the suppression of exon 7 in nonmuscle cells when flanked by heterologous exons derived from adenovirus. We have also shown by both in vivo and in vitro assays that the blockage of exon 7 in nonmuscle cells is primarily at its 3'-splice site. A model is presented for regulated alternative splicing in both skeletal muscle and nonmuscle cells.

Alternative Splicing↗

PubMed2003

Conserved sequence elements associated with exon skipping.

One of the major forms of alternative splicing, which generates multiple mRNA isoforms differing in the precise combinations of their exon sequences, is exon skipping. While in constitutive splicing all exons are included, in the skipped pattern(s) one or more exons are skipped. The regulation of this process is still not well understood; so far, cis- regulatory elements (such as exonic splicing enhancers) were identified in individual cases. We therefore set to investigate the possibility that exon skipping is controlled by sequences in the adjacent introns. We employed a computer analysis on 54 sequences documented as undergoing exon skipping, and identified two motifs both in the upstream and downstream introns of the skipped exons. One motif is highly enriched in pyrimidines (mostly C residues), and the other motif is highly enriched in purines (mostly G residues). The two motifs differ from the known cis-elements present at the 5' and 3' splice site. Interestingly, the two motifs are complementary, and their relative positional order is conserved in the flanking introns. These suggest that base pairing interactions can underlie a mechanism that involves secondary structure to regulate exon skipping. Remarkably, the two motifs are conserved in mouse orthologous genes that undergo exon skipping.

Alternative Splicing↗

PubMed1999

Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene.

In the rat beta-tropomyosin (beta-TM) gene, exons 6 and 7 are spliced alternatively in a mutually exclusive manner. Exon 6 is included in mRNA encoding nonmuscle TM-1, whereas exon 7 is used in mRNA encoding skeletal muscle beta-TM. Previously, we demonstrated that a six nucleotide mutation at the 5' end of exon 7, designated as ex-1, activated exon 7 splicing in nonmuscle cells. In this study, we show that the activating effect of this mutation is not the result of creating an exonic splicing enhancer (ESE) or disrupting a putative secondary structure. The sequence in exon 7 acts as a bona fide exonic splicing silencer (ESS), which is bound specifically by a trans-acting factor. Isolation and peptide sequencing reveal that this factor is hnRNP H, a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. Binding of hnRNP H correlates with the ESS activity. Furthermore, addition of antibodies that specifically recognizes hnRNP H to the splicing reactions or partial depletion of hnRNP H from nuclear extract activates exon 7 splicing in vitro and this effect can be reversed by addition of purified recombinant hnRNP H. These results indicate that hnRNP H participates in exclusion of exon 7 in nonmuscle cells. The involvement of hnRNP H in the activity of an ESS may represent a prototype for the regulation of tissue- and developmental-specific alternative splicing.

Alternative Splicing↗

PubMed2001

The contribution of exon-skipping events on chromosome 22 to protein coding diversity.

Completion of the human genome sequence provides evidence for a gene count with lower bound 30,000-40,000. Significant protein complexity may derive in part from multiple transcript isoforms. Recent EST based studies have revealed that alternate transcription, including alternative splicing, polyadenylation and transcription start sites, occurs within at least 30-40% of human genes. Transcript form surveys have yet to integrate the genomic context, expression, frequency, and contribution to protein diversity of isoform variation. We determine here the degree to which protein coding diversity may be influenced by alternate expression of transcripts by exhaustive manual confirmation of genome sequence annotation, and comparison to available transcript data to accurately associate skipped exon isoforms with genomic sequence. Relative expression levels of transcripts are estimated from EST database representation. The rigorous in silico method accurately identifies exon skipping using verified genome sequence. 545 genes have been studied in this first hand-curated assessment of exon skipping on chromosome 22. Combining manual assessment with software screening of exon boundaries provides a highly accurate and internally consistent indication of skipping frequency. 57 of 62 exon skipping events occur in the protein coding regions of 52 genes. A single gene, (FBXO7) expresses an exon repetition. 59% of highly represented multi-exon genes are likely to express exon-skipped isoforms in ratios that vary from 1:1 to 1:>100. The proportion of all transcripts corresponding to multi-exon genes that exhibit an exon skip is estimated to be 5%.

Alternative Splicing↗

PubMed1996

Structure of the human alpha 2 subunit gene of the glycine receptor--use of vectorette and Alu-exon PCR.

The alpha subunit of the glycine receptor is encoded by multiple genes that display developmental and tissue-specific expression. The alpha 1 subunit gene is expressed predominantly in the adult brain stem and spinal cord, whereas the alpha 2 subunit gene is expressed in fetal brain and spinal cord. We wished to determine the genomic organization of the human alpha 2 subunit gene as well as to define the 5' ends of the alpha 1 and alpha 2 subunit genes. Gene structure can be defined rapidly from yeast artificial chromosome (YAC) DNA sources by the use of vectorette-exon polymerase chain reaction (PCR). However, YACs frequently contain small deletions that complicate the determination of the complete exon-intron structure of a gene, and this often necessitates the isolation of additional clones. In this study we have used vectorette-exon PCR from YAC DNA to define exons of the glycine receptor alpha 2 subunit gene. To define those exons that were absent in the isolated YACs, we used Alu-exon PCR on genomic DNA, using nested primers to obtain specificity in the PCR reactions. The alpha 2 subunit gene was found to contain nine exons varying in size from 68 bp (exons 3A and 3B) to 581 bp (exon l). All of the intron-exon boundary sequences conform to consensus splice donor and acceptor sites. In addition, we have defined the 5' end of this gene as well as that of the alpha 1 subunit gene by RACE-PCR. The structures of the alpha subunit glycine receptor genes in humans are very similar to each other and to the alpha subunit genes in mice.

Base Sequence↗

PubMed2004

Ambiguities of human leukocyte antigen-B resolved by sequence-based typing of exons 1, 4, and 5.

The elucidation of the sequences of human leukocyte antigen-B (HLA-B)-exons 1 through 5 has led to an increase of ambiguities with alleles having identical exon 2 and 3 sequences, but differences in other exons. At the moment, 26 HLA-B alleles show such ambiguities which can be resolved by sequencing the exons in which the differences are located. Here we report a sequence-based typing (SBT) strategy for heterozygous sequencing of exons 1, 4, and 5, in addition to the previously described exons 2 and 3. The strategy was validated against a panel of 25 individuals, carrying HLA-B alleles from 33 different allele groups. Correct assignment of all HLA-B alleles was obtained for exons 1 through 5. In addition, the SBT protocol was used to resolve ambiguities in 50 individuals. The ambiguous combinations studied were B*0705/06, B*0801/19N, B*1512/19, B*180101/17N, B*270502/13/0504, B*350101/42/40N, B*390101/0103, B*400102/0101, B*440201/19N/27, and B*510101/11N/0105/30/32. In all cases, sequencing revealed the first allele to be present, except for three individuals with B*07. One of them typed B*0705; the other two were B*0706. The described SBT protocol for sequencing exons 1, 4, and 5 is a valuable tool for resolving ambiguities of HLA-B alleles with differences in these exons, as well as for studying the polymorphism of HLA-B outside exons 2 and 3.

Base Sequence↗

PubMed1990

Exon as well as intron sequences are cis-regulating elements for the mutually exclusive alternative splicing of the beta tropomyosin gene.

The beta tropomyosin gene contains two internal exons which are spliced in a mutually exclusive manner. Exon 6B is specifically included in the mature transcripts expressed in skeletal muscle or cultured myotubes, while exon 6A is a myoblast- or smooth muscle-specific exon. The intron between them, which is never spliced in normal conditions, contains two characteristic features: first, the unusual location of the branch point at position -105 from the acceptor, and second, the presence of a very long pyrimidine stretch upstream of the skeletal muscle exon. In this study we designed a number of sequence modifications to investigate the role of these two elements and of a computer-predicted secondary structure in the mutually exclusive splicing of the two exons. We found that mutations in the skeletal exon as well as in the upstream intron could change in vivo the tissue-specific pattern as well as the mutually exclusive character of the two exons. Our results suggest that the unusual position of the branch point does not prevent the utilization of exon 6B in myoblasts and that the region around the acceptor site of exon 6B and the polypyrimidine tract have an important role in this control. Last, we discuss the possible implications of secondary structures.

Animals↗

PubMed1996

Muscle-specific splicing enhancers regulate inclusion of the cardiac troponin T alternative exon in embryonic skeletal muscle.

The alternative exon 5 of the striated muscle-specific cardiac troponin T (cTNT) gene is included in mRNA from embryonic skeletal and cardiac muscle and excluded in mRNA from the adult. The embryonic splicing pattern is reproduced in primary skeletal muscle cultures for both the endogenous gene and transiently transfected minigenes, whereas in nonmuscle cell lines, minigenes express a default exon skipping pattern. Using this experimental system, we previously showed that a purine-rich splicing enhancer in the alternative exon functions as a constitutive splicing element but not as a target for factors regulating cell-specific splicing. In this study, we identify four intron elements, one located upstream,and three located downstream of the alternative exon, which act in a positive manner to mediate the embryonic splicing pattern of exon inclusion. Synergistic interactions between at least three of the four elements are necessary and sufficient to regulate splicing of a heterologous alternative exon and heterologous splice sites. Mutations in these elements prevent activation of exon inclusion in muscle cells but do not affect the default level of exon inclusion in nonmuscle cells. Therefore, these elements function as muscle-specific splicing enhancers (MSEs) and are the first muscle-specific positive-acting splicing elements to be described. One MSE located downstream from the alternative exon is conserved in the rat and chicken cTNT genes. A related sequence is found in a third muscle-specific gene, that encoding skeletal troponin T, downstream from an alternative exon with a developmental pattern of alternative splicing similar to that of rat and chicken cTNT. Therefore, the MSEs identified in the cTNT gene may play a role in developmentally regulated alternative splicing in a number of different genes.

Alternative Splicing↗

PubMed1997

A complex intronic splicing enhancer from the c-src pre-mRNA activates inclusion of a heterologous exon.

The mouse c-src gene contains a short neuron-specific exon, N1. To characterize the sequences that regulate N1 splicing, we used a heterologous gene, derived from the human beta-globin gene, containing a short internal exon that is usually skipped by the splicing machinery. Various fragments from the src gene were inserted into the globin substrate to measure their effects on the splicing of the test exon. These clones were transiently expressed in neuronal and nonneuronal cell lines, and the level of exon inclusion was measured by primer extension. Several sequences from the N1 exon region induced the splicing of the heterologous exon. The most powerful effect was seen with a sequence from the intron downstream of the N1 exon. This sequence acted as a strong splicing enhancer, activating splicing of the test exon when placed in the intron downstream. The enhancer was strongest in neuronal LA-N-5 cells but also activated splicing in nonneuronal HEK293 cells. Deletion and linker scanning mutagenesis indicate that the enhancer is made up of multiple smaller elements that must act in combination. One of these elements was identified as the sequence UGCAUG. Three copies of this element can strongly activate splicing of the test exon in LA-N-5 neuroblastoma cells. These component elements of the src splicing enhancer are also apparently involved in the splicing of other short cassette exons.

Animals↗

PubMed1989

Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons.

The single-copy Drosophila muscle myosin heavy-chain (MHC) gene, located at 36B(2L), has a complex exon structure that produces a diversity of larval and adult muscle MHC isoforms through regulated alternative RNA splicing. Genomic and cDNA sequence analyses revealed that this 21-kilobase MHC gene encodes these MHC isoforms in 19 exons. However, five sets of these exons, encoding portions of the S1 head and the hinge domains of the MHC protein, are tandemly repeated as two, three, four, or five divergent copies, which are individually spliced into RNA transcripts. RNA hybridization studies with exon-specific probes showed that at least 10 of the 480 possible MHC isoforms that could arise by alternative RNA splicing of these exons are expressed as MHC transcripts and that the expression of specific members of alternative exon sets is regulated, both in stage and in muscle-type specificity. This regulated expression of specific exons is of particular interest because the alternatively spliced exon sets encode discrete domains of the MHC protein that likely contribute to the specialized contractile activities of different Drosophila muscle types. The alternative exon structure of the Drosophila MHC gene and the single-copy nature of this gene in the Drosophila genome make possible transgenic experiments to test the physiological functions of specific MHC protein domains and genetic and molecular experiments to investigate the mechanisms that regulate alternative exon splicing of MHC and other muscle gene transcripts.

Amino Acid Sequence↗