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Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin.

The region of tenascin-C containing only alternately spliced fibronectin type-III repeat D (fnD) increases neurite outgrowth by itself and also as part of tenascin-C. We previously localized the active site within fnD to an eight amino acid sequence unique to tenascin-C, VFDNFVLK, and showed that the amino acids FD and FV are required for activity. The purpose of this study was to identify the neuronal receptor that interacts with VFDNFVLK and to investigate the hypothesis that FD and FV are important for receptor binding. Function-blocking antibodies against both alpha7 and beta1 integrin subunits were found to abolish VFDNFVLK-mediated process extension from cerebellar granule neurons. VFDNFVLK but not its mutant, VSPNGSLK, induced clustering of neuronal beta1 integrin immunoreactivity. This strongly implicates FD and FV as important structural elements for receptor activation. Moreover, biochemical experiments revealed an association of the alpha7beta1 integrin with tenascin-C peptides containing the VFDNFVLK sequence but not with peptides with alterations in FD and/or FV. These findings are the first to provide evidence that the alpha7beta1 integrin mediates a response to tenascin-C and the first to demonstrate a functional role for the alpha7beta1 integrin receptor in CNS neurons.

Alternative Splicing↗

Gene structure for the alpha 1 chain of a human short-chain collagen (type XIII) with alternatively spliced transcripts and translation termination codon at the 5' end of the last exon.

Two overlapping human genomic clones that encode a short-chain collagen, designated alpha 1(XIII), were isolated by using recently described cDNA clones. Characterization of the cosmid clones that span approximately equal to 65,000 base pairs (bp) of the 3' end of the gene established several unusual features of this collagen gene. The last exon encodes solely the 3' untranslated region and it begins with a complete stop codon. The 10 adjacent exons vary in size from 27 to 87 bp and two of them are 54 bp. Therefore, the alpha 1-chain gene of type XIII collagen has some features found in genes for fibrillar collagens but other features that are distinctly different. Previous analysis of overlapping cDNA clones and nuclease S1 mapping of mRNAs indicated one alternative splicing site causing a deletion of 36 bp from the mature mRNA. The present study showed that the 36 bp is contained within the gene as a single exon and also that the gene has a 45-bp -Gly-Xaa-Xaa- repeat coding exon not found in the cDNA clones previously characterized. Nuclease S1 mapping experiments indicated that this 45-bp exon is found in normal human skin fibroblast mRNAs. Accordingly, the data demonstrate that there is alternative splicing of at least two exons of the type alpha 1(XIII)-chain gene.

Base Sequence↗

Rat cystathionine beta-synthase: expression of four alternatively spliced isoforms in transfected cultured cells.

The gene for rat cystathionine beta-synthase consists of 17 exons. Its transcripts are alternatively spliced, forming four distinct mRNA species. Type III consists of exons 1 through 12, 14, 15, and 17; type I also contains exon 16. The open reading frame of type IV spans exons 1-->13; type II, 3-->13. We cloned the corresponding cDNAs into appropriate expression vectors and inserted the constructs into Escherichia coli (I, III, and IV) and Chinese hamster (CH) cells (I through IV); all sequences were transcribed and translated. Catalytic activity was observed only for types I and III in lysates of transfected CH cells and transformed E. coli. The catalytic and kinetic properties of I and III were identical despite their structural difference (exon 16). Both isoforms exhibited 6 mM Km constants for homocysteine which were reduced approximately eightfold by AdoMet; this elucidates the mechanism by which AdoMet regulates synthase activity. The four isoforms were differentially degraded by transfected cultured cells. Type III (t1/2 = 18 h) was degraded at 1/3 the rate of type I (t1/2 = 6 h); thus the 14 amino acid residues encoded by exon 16 appear to enhance degradation of CBS. The half-lives of both types II and IV were markedly shorter (ca. 1 h). Western blots comparing rat liver to lysates from transfected CH cells revealed that hepatocytes express both isoforms. Type III was predominant, as predicted by its longer half-life and more abundant mRNA. PCR analysis of cDNA from various tissues revealed that type III mRNA was preferred in liver, kidney, and heart; equal amounts of I and III were found in brain.

Alternative Splicing↗

Alternative splicing and endoproteolytic processing generate tissue-specific forms of pituitary peptidylglycine alpha-amidating monooxygenase (PAM).

The pituitary is a rich source of peptidylglycine alpha-amidating monooxygenase (PAM). This bifunctional protein contains peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalytic domains necessary for the two-step formation of alpha-amidated peptides from their peptidylglycine precursors. In addition to the four forms of PAM mRNA identified previously, three novel forms of PAM mRNA were identified by examining anterior and neurointermediate pituitary cDNA libraries. None of the PAM cDNAs found in pituitary cDNA libraries contained exon A, the 315-nucleotide (nt) segment situated between the PHM and PAL domains and present in rPAM-1 but absent from rPAM-2. Although mRNAs of the rPAM-3a and -3b type encode bifunctional PAM precursors, the proteins differ significantly. rPAM-3b lacks a 54-nt segment encoding an 18-amino acid peptide predicted to occur in the cytoplasmic domain of this integral membrane protein; rPAM-3a lacks a 204-nt segment including the transmembrane domain and encodes a soluble protein. rPAM-5 is identical to rPAM-1 through nt 1217 in the PHM domain; alternative splicing generates a novel 3'-region encoding a COOH-terminal pentapeptide followed by 1.1 kb of 3'-untranslated region. The soluble rPAM-5 protein lacks PAL, transmembrane, and cytoplasmic domains. These three forms of PAM mRNA can be generated by alternative splicing. The major forms of PAM mRNA in both lobes of the pituitary are rPAM-3b and rPAM-2. Despite the fact that anterior and neurointermediate pituitary contain a similar distribution of forms of PAM mRNA, the distribution of PAM proteins in the two lobes of the pituitary is quite different. Although integral membrane proteins similar to rPAM-2 and rPAM-3b are major components of anterior pituitary granules, the PAM proteins in the neurointermediate lobe have undergone more extensive endoproteolytic processing, and a 75-kDa protein containing both PHM and PAL domains predominates. The bifunctional PAM precursor undergoes tissue-specific endoproteolytic cleavage reminiscent of the processing of prohormones.

Amino Acid Sequence↗

Alternatively spliced mRNAs predicted to yield frame-shift proteins and stable intron 1 RNAs of the herpes simplex virus 1 regulatory gene alpha 0 accumulate in the cytoplasm of infected cells.

The infected cell protein no. 0 (ICP0), the product of the alpha 0 gene, and an important herpes simplex virus 1 regulatory protein is encoded by three exons. We report that intron 1 forms a family of four stable nonpolyadenylylated cytoplasmic RNAs sharing a common 5' end but differing in 3' ends. The 5' and 3' ends correspond to the accepted splice donor and four splice acceptor sites within the mapped intron domain. The most distant splice acceptor site yields the mRNA encoding the 775-aa protein known as ICP0. The mRNAs resulting from the use of alternative splice acceptor sites were also present in the cytoplasm of infected cells and would be predicted to encode proteins of 152 (ICP0-B), 87 (ICP0-C), and 90 (ICP0-D) amino acids, respectively. Both the stability of the alpha 0 mRNA and the utilization of at least one splice acceptor site was regulated by ICP22 and or US1.5 protein inasmuch as cells infected with a mutant from which these genes had been deleted accumulated smaller amounts of alpha 0 mRNA than would be predicted from the amounts of accumulated intron RNAs. In addition, one splice acceptor site was at best underutilized. These results indicate that both the splicing pattern and longevity of alpha 0 mRNA are regulated. These and other recent examples indicate that herpes simplex virus 1 regulates its own gene expression and that of the infected cells through control of mRNA splicing and longevity.

Alternative Splicing↗

Myoadenylate deaminase deficiency caused by alternative splicing due to a novel intronic mutation in the AMPD1 gene.

We have examined two Caucasian brothers with myoadenylate deaminase (AMPD) deficiency who presented with exercise intolerance and muscle cramps. Allele-specific PCR amplification assays demonstrated that the common Q12X (C34T) and P48L (C143T) mutations were not found within their AMPD1 genes. Further analysis revealed that both brothers were compound heterozygotes for a previously reported K287I (A860T) mutation in exon 7 and a novel deletion within intron 2 (IVS2-(4-7)delCTTT). The intronic deletion appears to affect the splicing machinery since characterization of AMPD1 mRNA from skeletal muscle of one brother identified multiple alternatively spliced transcripts resulting in multiple deletions in exon 3, the complete deletion of either exon 3 or exons 3 and 4, and the activation of a cryptic splice site that resulted in an insertion at the 5' end of exon 4. The predominant transcript contains a 51 base deletion at the 5' end of exon 3 that is predicted to produce a functional form of AMPD containing a 17-amino acid residue deletion within its N-terminal region. Analysis of 137 Caucasian normal control patients determined that the K287I mutation is relatively frequent (5.1% carrier frequency), whereas the IVS2-(4-7)delCTTT mutation is rare and not present in 274 chromosomes.

AMP Deaminase↗

The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing.

Tropomyosin (TM), a ubiquitous protein, is a component of the contractile apparatus of all cells. In nonmuscle cells, it is found in stress fibers, while in sarcomeric and nonsarcomeric muscle, it is a component of the thin filament. Several different TM isoforms specific for nonmuscle cells and different types of muscle cell have been described. As for other contractile proteins, it was assumed that smooth, striated, and nonmuscle isoforms were each encoded by different sets of genes. Through the use of S1 nuclease mapping, RNA blots, and 5' extension analyses, we showed that the rat alpha-TM gene, whose expression was until now considered to be restricted to muscle cells, generates many different tissue-specific isoforms. The promoter of the gene appears to be very similar to other housekeeping promoters in both its pattern of utilization, being active in most cell types, and its lack of any canonical sequence elements. The rat alpha-TM gene is split into at least 13 exons, 7 of which are alternatively spliced in a tissue-specific manner. This gene arrangement, which also includes two different 3' ends, generates a minimum of six different mRNAs each with the capacity to code for a different protein. These distinct TM isoforms are expressed specifically in nonmuscle and smooth and striated (cardiac and skeletal) muscle cells. The tissue-specific expression and developmental regulation of these isoforms is, therefore, produced by alternative mRNA processing. Moreover, structural and sequence comparisons among TM genes from different phyla suggest that alternative splicing is evolutionarily a very old event that played an important role in gene evolution and might have appeared concomitantly with or even before constitutive splicing.

Amino Acid Sequence↗

Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression.

Sequence-based analyses have predicted that approximately 35% of mammalian alternative splicing (AS) events produce premature termination codon (PTC)-containing splice variants that are targeted by the process of nonsense-mediated mRNA decay (NMD). This led to speculation that AS may often regulate gene expression by activating NMD. Using AS microarrays, we show that PTC-containing splice variants are generally produced at uniformly low levels across diverse mammalian cells and tissues, independently of the action of NMD. Our results suggest that most PTC-introducing AS events are not under positive selection pressure and therefore may not contribute important functional roles.

Alternative Splicing↗

Deregulated alternative splicing of CD44 messenger RNA transcripts in neoplastic and nonneoplastic lesions of the human thyroid.

CD44 is a polymorphic family of immunologically related cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, lymphocyte activation and homing, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms, each generated by alternative splicing of up to 10 variant exons (termed v1-v10) encoding parts of the extracellular domain. Using semiquantitative reverse transcriptase-PCR and Southern hybridization, alternative CD44 mRNA splicing was examined in 10 papillary thyroid carcinomas, 8 nodular goiters, 9 adenomas, 2 cases of thyroiditis, and 3 histologically normal thyroid controls. The amount of input cDNA for the CD44 PCRs was standardized against an internal control gene (glyceraldehyde phosphate dehydrogenase). Four papillary carcinomas showed significant overexpression of CD44 transcripts migrating between 750 and 1000 bp. These cases demonstrated reduced levels of the 482-bp standard isoform transcript. In six papillary cancers, we found a prominent v6-containing isoform at 750 bp that was present in only trace amounts in normal thyroid tissue. It is of interest that similar findings were seen in the majority of the goiters and adenomas but not in the cases of thyroiditis. These results show that deregulation of alternative CD44 splicing is a common feature of disordered thyroid follicular cell growth, both in neoplastic and nonneoplastic lesions. The data imply an important role for CD44, including CD44v6, in the pathogenesis of various thyroid lesions.

Adenocarcinoma, Papillary↗

Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions.

Agrin is a protein implicated in the formation and maintenance of the neuromuscular junction. In addition to motor neurons, agrin mRNA has been detected in the brains of embryonic rat and chick and adult marine ray, suggesting that this molecule may also be involved in the formation of synapses between neurons. As a step toward understanding agrin's role in the CNS, we utilized Northern blot and in situ hybridization techniques to analyze the regional distribution and cellular localization of agrin mRNA in the spinal cord and brain of adult rats. The results of these studies indicate that the agrin mRNA is expressed predominantly by neurons broadly distributed throughout the adult CNS. Moreover, expression of agrin mRNA is not restricted to cholinergic structures or regions of the brain receiving cholinergic input. Recently, RNA isolated from rat embryonic spinal cord was shown to contain four alternatively spliced agrin mRNAs, referred to as agrin0, agrin8, agrin11, and agrin19, each of which encodes agrin proteins that are active in acetylcholine receptor aggregating assays (Ferns et al., 1992). Using the polymerase chain reaction we demonstrate that all four of these agrin transcripts are expressed within the adult CNS. Agrin0, agrin8, and agrin19 were present in all regions analyzed. In contrast, agrin11 was detected only in forebrain. Results of these studies indicate that both the level of expression and pattern of alternative splicing of agrin mRNA are differentially regulated in the brain. The broad and predominantly neuronal distribution of agrin mRNA in the adult brain suggests that, in addition to its role at the neuromuscular junction, agrin may play a role in formation and maintenance of synapses between neurons in the CNS.

Agrin↗

Regulation of Slo potassium channel alternative splicing in the pituitary by gonadal testosterone.

Slo gene-encoded BK potassium channels are prominent in both adrenomedullary and pituitary tissues. At one alternative splicing site, both tissues express variants with and without the optional 'STREX' exon. In adrenal chromaffin cells, this splicing choice, which has important ramifications for cell excitability, has been shown to be regulated by steroid hormones, including glucocorticoids and adrenal androgens. Moreover, striking sex differences are seen between male and female tree shrews. Here, we test the hypothesis that gonadal testosterone regulates splicing in these tissues. No significant sex differences were found in rats, in either adrenals or pituitaries. In the adrenal medulla, prepubertal castration in male rats increased the relative abundance of STREX transcripts slightly, but not significantly, as measured several weeks after puberty. However, castration substantially decreased STREX representation in the rat pituitary. Silastic implants of testosterone inserted at castration prevented this STREX decline. In postpubescent males, castration or T implants had less effect. Thus, we report (i) steroidal regulation of Slo splicing in the pituitary and (ii) participation of the male gonads in this regulation.

Adrenal Medulla↗

Chondroitin sulphate composition and structure in alternatively spliced CD44 fusion proteins.

Previous studies have indicated that CD44 isoforms, spliced with variant exons, are heterogeneously glycanated with chondroitin sulphate and heparan sulphate chains. Because such alternative splicing may regulate divergent biological effects of the specific isoforms, we analysed the consequences of this process on the composition and structure of the chondroitin-sulphate chains. Recombinant chimaeras were engineered with and without exons V3-10 or V3,8-10 and expressed as Ig fusion proteins in COS cells. In addition, the chondroitin sulphates of wild-type isoforms were contrasted with those of isoforms mutated with serine-to-alanine codon substitutions at a putative Ser-Gly-Ser-Gly glycosaminoglycan acceptor site within exon V3. The chondroitin sulphates contained both 4- and 6-sulphated galactosamine residues, although there was a high content of non-sulphated galactosamine-containing repeat units. Splicing of exons V4-7, which contain no Ser-Gly consensus motifs, resulted in increased glycanation with chondroitin-sulphate chains, as well as increased sulphation levels of the polymers. Comparison of wild-type and acceptor-site mutant isoforms showed that chondroitin-sulphate content declined by more than 60-80% in the mutant, indicating that assembly of chondroitin-sulphate chains occurs there, and a general decrease in the sulphation level of the remaining chains was observed. Undersulphation of the recombinant chondroitin sulphates was shown by parallel analyses with native human keratinocyte CD44 molecules and is most probably an artifact of transient expression in COS cells. Our data indicate that combinatorial exon splicing exerts complex and distal effects on glycanation patterns and structure, which presumably modulate those functions that may be mediated though the chondroitin-sulphate moieties, such as motility and matrix invasion.

Alternative Splicing↗

Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype.

Membrane cofactor protein (MCP) is a complement regulatory protein that is expressed on human cells and cell lines as two relatively broad species with Mr of 58,000-68,000 and 48,000-56,000. The structure of a previously reported cDNA clone indicated that MCP was a type 1 membrane glycoprotein and a member of the regulators of complement activation gene/protein cluster. However, it did not provide an explanation for the unusual phenotypic pattern of MCP. Therefore, in parallel with an analysis of the gene, additional cDNAs were cloned and characterized. Six different MCP cDNA classes were identified. All encode the same 5' untranslated signal peptide, four SCRs, transmembrane domain, and basic amino acid anchor. However, they differ in the length and composition of an extracellular serine/threonine/proline (STP)-rich area, a site of heavy O-glycosylation, and cytoplasmic tail. Analysis of the MCP gene demonstrated that the variation in cDNA structure was a result of alternative splicing. Peripheral blood cells and cell lines predominantly expressed four of the six isoforms. These varied by the presence or absence of an STP-rich segment of 15 amino acids (STPB) and by the use of one of two cytoplasmic domains. Analysis by polymerase chain reaction, Northern blots, and transfection indicated that the predominance of MCP cDNA isoforms with STPB correlated with the high molecular weight protein phenotype, while the predominance of isoforms without STPB correlated with the lower molecular weight phenotype. The expression in a single cell of four distinct protein species with variable STP-rich regions and cytoplasmic tails represents an interesting example of the use of alternative splicing to provide variability in a mammalian protein.

Amino Acid Sequence↗

Physiologically regulated alternative splicing patterns of fast troponin T RNA are conserved in mammals.

NH2-terminal isoforms of fast troponin T (TnT) are generated by alternative splicing of fast TnT RNA transcripts. Significantly different estimates for the number of isoforms have been obtained by nucleic acid and protein chemical studies. To resolve this controversy and to determine whether specific 5'-splicing patterns correlate with fiber phenotype, we generated representative populations of 5'-TnT cDNAs from the TnT mRNAs expressed in a set of physiologically and anatomically diverse skeletal muscles. Sequencing and restriction enzyme analyses revealed a total of nine cDNAs that encode the six adult and three perinatal NH2-terminal TnT variants previously identified. Three major 5'-splicing pathways (the TnT1f, TnT2f, and TnT3f patterns) account for more than 90% of the TnT mRNAs and proteins in adult rabbit skeletal muscle. Comparative studies in rats, mice, and humans show that these splicing patterns are conserved and that fast-twitch fibers that are primarily glycolytic utilize the TnT1f and TnT2f patterns preferentially, whereas fast-twitch fibers that are primarily oxidative use the TnT1f and TnT3f patterns preferentially.

Alternative Splicing↗

Neuroprotection associated with alternative splicing of NMDA receptors in rat cortical neurons.

Exposure of cultured cortical neurons to elevated extracellular K(+) concentrations (25 mM) induces membrane depolarization and an increase in action-potential firing. Long-term high K(+) treatment was associated with an increased neuronal cell death. In surviving neurons, multiple changes occurred in the proportion of individual NMDA receptor subunit 1 (NR1) splice variant mRNA expression, whereas the overall expression of NR1, NR2A and NR2B transcripts remained unaffected. The high K(+)-induced changes in NR1 splice variant expression were virtually abolished upon a concurrent administration of tetrodotoxin (TTX; 3 microM). In voltage-clamp recordings performed on neurons resistant to high K(+) treatment, inward currents induced by NMDA (1-1,000 microM) were reduced. In K(+)-resistant cells, the activity of calpain but not of caspase-3 was diminished compared with controls kept in regular medium. NR function as well as calpain activity was not affected in cultures concomitantly treated with high K(+) and either TTX or a NR antagonist (CGS19755 (selfotel) or memantine). In conclusion, the present data indicate adaptive changes in NR1 splice variant expression and a decrease in NR function upon a sustained increase in neurotransmission. Accordingly, alternative splicing could be an endogenous mechanism to counteract cellular damage due to overactivation of excitatory NRs and may be associated with an impairment of necrotic mechanisms.

Action Potentials↗

Expression and functional significance of alternatively spliced CS1 fibronectin in rheumatoid arthritis microvasculature.

Expression of fibronectin (FN) isoforms containing CS1, a 25-amino acid sequence present within the alternatively spliced IIICS region of FN, has been analyzed in rheumatoid arthritis (RA) synovium. Unexpectedly, CS1-containing FN variants were exclusively found on endothelium but not extracellular matrix (ECM) of RA synovium. Lumenal expression of CS1 on RA endothelial cells, as observed by electron microscopy, correlated with inflammation in RA, since normal synovium expressed little CS1 without appreciable decrease in ECM FN. CS1 expression on human endothelial cells was further shown by FN mRNA analyses. In adhesion assays on frozen RA synovial sections, T lymphoblastoid cells expressing functionally activated alpha 4 beta 1 integrin specifically attached to the intravascular surface of RA endothelium. Binding was abrogated by both anti-alpha 4 integrin and CS1 peptides. Our observations suggest direct involvement of CS1-containing FN in recruitment of alpha 4 beta 1-expressing mononuclear leukocytes in synovitis, and provide basis for therapeutic intervention in RA.

Alternative Splicing↗

Tissue-specific expression of two alternatively spliced isoforms of the human insulin receptor protein.

Two insulin receptor mRNA species are expressed in human tissues as a result of alternative splicing of exon 11. This event is regulated in a tissue-specific manner. To date, there is little information about the relative abundance of the two receptor protein isoforms on the cell surface. The aim of the present investigation was to assess whether the tissue-specific expression of the two insulin receptor mRNA species is paralleled by a similar pattern of expression of the two receptor protein isoforms. To this end, we assessed the relative distribution of the two receptor variants in various human tissues at the mRNA and protein levels. A PCR-based technique was used to measure the relative abundance of the two mRNA species, and two immunological assays were used to measure the relative steady-state expression of the two receptor protein isoforms. The expression of the two insulin receptor protein isoforms followed the tissue-specific pattern of expression of the two mRNA species.

3T3 Cells↗

Characterization of new human c-myc mRNA species produced by alternative splicing.

Characterization of two human c-myc cDNAs corresponding to the mRNAs 2.5 and 3.1 kb in length transcribed from P0 previously demonstrated the existence of alternative acceptor sites at the end of intron 1 and intron 2, respectively [Bentley, D.L. and Groudine, M. (1986) Mol. Cell. Biol. 6, 3481-3489]. We investigated the use of these alternative acceptor sites in each c-myc mRNA species. We characterized cDNAs corresponding to c-myc mRNAs transcribed in the SW613-S human carcinoma cell line. The use of the alternative acceptor site at the end of intron 1 was demonstrated in two out of 10 cDNAs corresponding to the 3.1-kb mRNA transcribed from P0 and in three out of 10 cDNAs corresponding to the mRNAs transcribed from P1 or P2. The use of this acceptor site is therefore not restricted to the 2.5-kb mRNA transcribed from P0. The mRNAs resulting from the use of this acceptor site is therefore not restricted to the 2.5-kb mRNA transcribed from P0. The mRNAs resulting from the use of this acceptor site would encode for a variant form of the p67 polypeptide lacking one amino-acid residue. Conversely, the use of the alternative acceptor site at the end of intron 2 was not found in any of the cDNAs corresponding to the mRNAs transcribed from P0 (0/10), from P1 or P2 (0/10) and from P3 (0/10). In the course of this study, we isolated a cDNA corresponding to another new c-myc mRNA species. This mRNA is produced by alternative splicing within intron 1 and encodes only for p64.

Alternative Splicing↗