SEARCH · PubMed Health

Results for “Alternative Splicing”

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 991 records · Page 55Linked to original sources

PubMed1989

Identification of the alternatively spliced exons of murine CD45 (T200) required for reactivity with B220 and other T200-restricted antibodies.

Cell lines expressing specific variants of murine CD45 (T200) were established by infection with retroviral constructs of four cDNAs encoding different forms of CD45. These lines were then used to determine which sequences encoded by alternatively spliced exons of CD45 were required to generate antigenic determinants recognized by anti-CD45 mAbs. The binding of two B220 antibodies (14.8 and RA32C2) to CD45 was dependent on the expression of the first alternatively spliced exon (exon A). A third B220 antibody, RA3-6B2, did not bind to any of the forms of CD45 expressed on fibroblasts. A newly defined anti-CD45R antibody, C363.16A, reacts with an antigenic site dependent upon the expression of the second alternatively spliced exon, exon B.

Animals↗

PubMed1999

Ca2+ and pH modulate alternative splicing of exon 5 in NMDA receptor subunit 1.

RT-PCR and intracellular Ca2+ measurements were used to identify factors that modulate alternative splicing of exon 5 in the NMDA receptor transcript encoding NR1, in cultured cerebellar granule neurons. Although cells grown in media containing 5 mM KCl demonstrate compromised survival, they show the predicted developmental transition from NR1a (-exon 5) to NR1b (+exon 5) mRNA expression. This transition was blocked under culture conditions that promote survival; inclusion or exclusion of exon 5 is a reversible process that is sensitive to alterations in Ca2+ and pH. We conclude that alternative splicing of NR1 pre-mRNA transcripts may be regulated by developmental cues that modulate the degree of glutamate receptor activation.

Alternative Splicing↗

PubMed1994

Conservation of regulated alternative splicing and identification of functional domains in vertebrate homologs to the Drosophila splicing regulator, suppressor-of-white-apricot.

Although several splicing regulatory proteins have been identified in Drosophila through characterization of various genetic mutations, including sex-lethal, transformer, transformer-2, suppressor-of-white-apricot (su(wa)), and possibly suppressor-of-sable, none of these have been identified in vertebrates. We describe the cloning and characterization of human (HsSWAP) and mouse (MmSWAP) homologs of the su(wa) gene. Comparison of the Drosophila and mammalian proteins reveals five highly homologous regions, including an arginine/serine-rich domain and two repeated modules that are homologous to regions in the constitutive splicing factor, SPP91/PRP21. These modules thus define a new motif likely important in the regulatory and constitutive splicing functions of these proteins. The Drosophila su(wa) gene autoregulates its expression by control of splicing of its first two introns. Comparison of mammalian and Drosophila SWAP mRNAs revealed that the splice junctions of these regulated introns are precisely conserved, showing definitively that these genes are ancestrally related. Moreover, mammalian SWAP mRNAs are also alternatively spliced at the same splice sites, showing that mammalian SWAP expression is regulated (presumably autogenously) by control of splicing of these two introns. These several structural features therefore strongly suggest that the mammalian SWAP gene functions as a vertebrate alternative splicing regulator.

Alternative Splicing↗

PubMed1998

A partial cDNA sequence of the ovine insulin receptor gene: evidence for alternative splicing of an exon 11 region and for tissue-specific regulation of receptor isoform expression in sheep muscle, adipose tissue and liver.

Insulin is as integral and important to the management of metabolism in ruminants as it is in non-ruminants. The suggestion of a lowered ruminant sensitivity and/or responsivity to insulin may relate more to the insulin receptor than to the hormone itself. We screened an ovine cDNA library using degenerate primers and polymerase chain reaction (PCR) to detect and sequence a cDNA portion corresponding to exons 10, 11 and 12 of the human insulin receptor gene in which a 36 base pair (bp) segment (exon 11) is alternatively spliced to produce two distinct receptor isoforms differing in functional characteristics including binding affinity for insulin. The ovine cDNA segment (nucleotides 671 to 770) displayed 84, 84, and 78% nucleotide homology to equivalent segments from the human, rhesus monkey and rat respectively. Reverse transcription PCR (RT-PCR) of selected tissues (liver, m. longissimus dorsi, m. rectus capitis and omental, perirenal and subcutaneous fats) taken at slaughter from three male, pure Dutch Texel lambs (experiment 1) and five male Texel-Greyface crossbred lambs (experiment 2) revealed two mRNA products in each tissue (including spleen; experiment 2 only) corresponding to cDNAs of molecular sizes 161 and 197 bp -- a difference of 36 bp. Sequence alignment showed the 36 bp segment to be homologous to the alternatively spliced exon 11 region of the human insulin receptor gene and to be highly conserved with that from other species. The abundance of the exon 11(+) isoform in the purebred Texel genotype was significantly higher in liver than in perirenal fat and rectus capitis and longissimus dorsi skeletal muscles (P<0.05) and higher also than in subcutaneous and omental fats (P<0.01). There was, however, no difference in the abundance of the exon 11(+) isoform between the individual muscle and fat depots in this sheep genotype. The abundance of the exon 11(+) isoform in the crossbred Texel genotype was significantly higher in liver (P<0. 05) than in the muscles (rectus capitis, P<0.05; longissimus dorsi, P<0.001), all three fats (P<0.001) and spleen (P<0.001). In the crossbred genotype, the abundance of the exon 11(+) isoform was higher in skeletal muscle than in all three fat depots (P<0.001), in which the isoform abundance was similar. Altered ratios of expression of the two products of this alternative splicing event could determine tissue sensitivity and/or responsivity to insulin and provide a mechanism for the management of nutrient partitioning and nutrient utilisation between tissues which is fundamental to the growth of tissues and manipulation of carcass characteristics in meat-producing animals.

Adipose Tissue↗

PubMed2006

Evidence that talin alternative splice variants from Ciona intestinalis have different roles in cell adhesion.

BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is essential for focal adhesion function, Talin2 is not targeted to focal adhesions. The nonvertebrate chordate Ciona intestinalis has only one talin gene, but alternative splicing of the talin mRNA produces two proteins with different C-terminal I/LWEQ modules. Thus, C. intestinalis contains two talins, Talin-a and Talin-b, with potentially different activities, despite having only one talin gene. RESULTS: We show here that, based on their distribution in cDNA libraries, Talin-a and Talin-b are differentially expressed during C. intestinalis development. The I/LWEQ modules of the two proteins also have different affinities for F-actin. Consistent with the hypothesis that Talin-a and Talin-b have different roles in cell adhesion, the distinct I/LWEQ modules of Talin-a and Talin-b possess different subcellular targeting determinants. The I/LWEQ module of Talin-a is targeted to focal adhesions, where it most likely serves as the link between integrin and the actin cytoskeleton. The Talin-b I/LWEQ module is not targeted to focal adhesions, but instead preferentially labels F-actin stress fibers. These different properties of C. intestinalis the Talin-a and Talin-b I/LWEQ modules mimic the differences between mammalian Talin1 and Talin2. CONCLUSION: Vertebrates and D. discoideum contain two talin genes that encode proteins with different functions. The urochordate C. intestinalis has a single talin gene but produces two separate talins by alternative splicing that vary in a domain crucial for talin function. This suggests that multicellular organisms require multiple talins as components of adhesion complexes. In C. intestinalis, alternative splicing, rather than gene duplication followed by neo-functionalization, accounts for the presence of multiple talins with different properties. Given that C. intestinalis is an excellent model system for chordate biology, the study of Talin-a and Talin-b will lead to a deeper understanding of cell adhesion in the chordate lineage and how talin functions have been parceled out to multiple proteins during metazoan evolution.

Actins↗

PubMed1992

A novel form of fibroblast growth factor receptor 2. Alternative splicing of the third immunoglobulin-like domain confers ligand binding specificity.

The fibroblast growth factor receptor 2 (FGFR2) gene is expressed as alternatively spliced mRNAs that encode bacterially expressed kinase, the keratinocyte growth factor receptor, or K-sam. We have now isolated a novel FGFR2 cDNA that is identical with the previously cloned human bacterially expressed kinase, except in the third immunoglobulin-like domain. The ligand binding properties of FGFR2 were studied by expressing the protein in rat L6 muscle myoblasts. Unlike human bacterially expressed kinase which binds acidic and basic FGF with similar affinities, FGFR2 bound acidic FGF with approximately 1000-fold higher affinity than basic FGF. These results indicate that alternative splicing of the FGFR2 gene in the region encoding the carboxyl-terminal half of the third immunoglobulin domain determines the ligand specificity of this group of receptors.

Alternative Splicing↗

PubMed2004

Alternative splice variant of actinin-4 in small cell lung cancer.

Tumor-associated alternative RNA splicing has gained considerable attention. We identified a novel alternative splice variant RNA of actinin-4 in human small cell lung cancer (SCLC). Expression of the splice variant was highly specific to SCLC cell lines (10/10), biopsies (3/3), and testis. The variant encoded a peptide with a three amino-acid change in exon 8, where the germline missense mutation takes place in familial focal segmental glomerulosclerosis (FSGS). The variant protein showed high affinity to filamentous actin polymers and was not localized with cortical actin. Alternatively spliced actinin-4 may be a new diagnostic marker of SCLC and a candidate target for selective therapy.

Actinin↗

PubMed1995

Chicken perinatal troponin Ts are generated by a combination of novel and phylogenetically conserved alternative splicing pathways.

During perinatal development, avian and mammalian skeletal muscles express a novel set of troponin T (TnT) isoforms with higher M(r)s and more acidic pIs than their adult counterparts. In mammals, these TnTs result from the incorporation of a developmentally regulated 5'-fetal exon into fast TnT mRNAs. To determine whether chicken perinatal TnTs are generated by a similar mechanism, we sequenced 40 chicken TnT 5'-cDNAs from perinatal and adult pectoralis. Evidence for five 5'-exons not present in the mammalian gene was found, including one, y, whose splicing is developmentally regulated. Although none of these new exons are homologous with the mammalian fetal exon, their alternative splicing, superimposed on three conserved splicing patterns of the phylogenetically shared 5'-exons, generates the chicken perinatal TnT isoforms. These observations indicate that chicken, and most likely other avian species, evolved an independent 5'-alternative splicing mechanism to generate perinatal TnTs that have the same biophysical, and presumably functional, properties as their mammalian homologs.

Aging↗

PubMed1998

Sequencing of two alternatively spliced mRNAs corresponding to the extracellular domain of the rat receptor for advanced glycosylation end products (RAGE).

The receptor for advanced glycosylation end products (RAGE) is an integral membrane protein responsible for the recognition and internalization of those extensively modified proteins. The receptor has an extracellular domain that binds to the advanced glycosylation end products. By reverse-transcription and polymerase chain reaction amplification, we have identified in rat liver and kidney two amplified products that correspond to cDNA coding for a part of the extracellular domain of the receptor. Sequencing of these products showed that these amplified molecules were similar except for a 27-bp fragment that was absent in the smaller product. This spliced region is located close to the transmembrane region of the receptor. We have confirmed the possibility of the alternative splicing in the generation of these mRNA isoforms by cloning a fragment of the rat gene for RAGE. This fragment has a distribution of introns and exons fully compatible with the proposed alternative splicing.

Alternative Splicing↗

PubMed1996

Alternative splicing of exon 3 of the human growth hormone receptor is the result of an unusual genetic polymorphism.

Two isoforms of the human growth hormone receptor (hGHR), which differ in the presence (hGHRwt) or absence (hGHRd3) of exon 3, are expressed in the placenta. Specifically, three expression patterns are observed: only hGHRwt, only hGHRd3, or an approximately 1:1 combination of both isoforms. We investigated several potential regulatory mechanisms which might account for the expression of the hGHR isoforms. The frequency of hGHRd3 expression did not change when placentas from differing stages of gestation were examined, suggesting splicing was not developmentally regulated. However, when hGHR isoform expression patterns were examined in each component of a given placenta, it was evident that alternative splicing of exon 3 is individual-specific. Surprisingly, the individual-specific regulation of hGHR isoforms appears to be the result of a polymorphism in the hGHR gene. We analyzed hGHRwt and hGHRd3 expression in Hutterite pedigrees, and our results are consistent with a simple Mendelian inheritance of two differing alleles in which exon 3 is spliced in an "all-or-none" fashion. We conclude the alternative splicing of exon 3 in hGHR transcripts is the result of an unusual polymorphism which significantly alters splicing of the hGHR transcript and that the relatively high frequency (approximately 10%) of homozygous hGHRd3 expression suggests the possibility it may play a role in polygenic determined events.

Alleles↗

PubMed1995

Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues.

We showed previously that the alternative splicing of chondroitin sulfate attachment domains (CS alpha and CS beta) yielded multiforms of the PG-M core protein in mouse. A transcript encoding a new short form of the core protein PG-M(V3) was found in various mouse tissues using polymerase chain reaction. DNA sequences of the polymerase chain reaction products suggested that PG-M(V3) had no chondroitin sulfate attachment domain. PG-M(V3) was also detected in various human tissues. The presence of a transcript for PG-M(V3) was further supported by Northern blot analysis. Southern blot analysis confirmed that multiforms of the PG-M core protein, including PG-M(V3), were derived from a single genomic locus by an alternative splicing mechanism. Because PG-M(V3) has no chondroitin sulfate attachment region, which is the most distinctive portion of a proteoglycan molecule, this form may have a unique function.

Alternative Splicing↗

PubMed1996

Alternative splicing of the Endo16 transcript produces differentially expressed mRNAs during sea urchin gastrulation.

The Endo16 gene codes for an RGD-containing calcium-binding protein that is found on the basal surfaces and in the extracellular matrix of cells of the invaginating archenteron during sea urchin gastrulation. Previously, we have shown that Endo16 is a single copy gene and we have determined the coding sequence and analyzed the temporal and spatial expression of a 6.6-kb mRNA. In this report we demonstrate that two additional longer Endo16 mRNAs are produced by differential splicing rather than alternative promoter usage. cDNA clones for two 8.5-kb mRNAs have been isolated and analyzed. The two 8.5-kb mRNAs are identical to each other in the coding region and differ only in their 3' UTRs. The extended open reading frame of the 8.5-kb mRNAs code for domains already identified in the 6.6-kb mRNA, including two different types of calcium-binding motifs and a region with a highly conserved cysteine pattern similar to that found in Ecm1 in the mouse. The 6.6- and 8.5-kb mRNAs show overlapping but distinct temporal as well as spatial expression patterns during gastrulation.

Alternative Splicing↗

PubMed1997

Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha.

We previously reported the cloning of a cDNA encoding human phosphatidylcholine-specific phospholipase D1 (PLD1), an ADP-ribosylation factor (ARF)-activated phosphatidylcholine-specific phospholipase D (Hammond, S. M., Tsung, S., Autschuller, Y., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and Frohman, M. A. (1995) J. Biol. Chem. 270, 29640-29643). We have now identified an evolutionarily conserved shorter splice variant of PLD1 lacking 38 amino acids (residues 585-624) that arises from regulated splicing of an alternate exon. Both forms of PLD1 (PLD1a and 1b) have been expressed in Sf9 cells using baculovirus vectors and purified to homogeneity by detergent extraction and immunoaffinity chromatography. PLD1a and 1b have very similar properties. PLD1a and 1b activity is Mg2+dependent but insensitive to changes in free Ca2+ concentration. Phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate activate PLD1a and 1b but a range of other acidic phospholipids are ineffective. PLD1a and 1b are highly responsive to activation by GTP-gammaS-liganded ADP-ribosylation factor-1 (ARF-1) and can also be activated to a lesser extent by three purified RHO family monomeric GTP-binding proteins, RHO A, RAC-1, and CDC42. Activation of PLD1a and 1b by the RHO family monomeric GTP-binding proteins is GTP-dependent and synergistic with ARF-1. Purified protein kinase C-alpha activates PLD1a and 1b in a manner that is stimulated by phorbol esters and does not require ATP. Activation of PLD1a and 1b by protein kinase C-alpha is synergistic with ARF and with the RHO family monomeric GTP-binding proteins, suggesting that these three classes of regulators interact with different sites on the enzyme.

Adenosine Diphosphate Ribose↗

PubMed2004

Alternatively spliced isoforms of fibronectin in immune-mediated glomerulosclerosis: the role of TGFbeta and IL-4.

Fibronectin (FN) is the main extracellular matrix component in glomerulosclerotic lesions. There are different FN isoforms that result from alternative splicing at the EDA and EDB regions of FN mRNA. Increased inclusion of EDA and EDB, which can be elicited by TGFbeta, may be conducive to the development of glomerulosclerosis (GS). TGFbeta and IL-4 have previously been shown to play a role in the development of GS. In this study, the mRNA splicing patterns for EDA+ and EDB+ fibronectin were investigated in vivo in various experimental sclerotic glomerulopathies, in vitro in rat mesangial cells (MC) that were stimulated by TGFbeta or transfected with IL-4, and in human kidney biopsies with GS from patients with various kidney diseases. Analysis of glomerular FN mRNA demonstrated inclusion of both ED regions in rats with anti-Thy1 nephritis or chronic serum sickness and in mice with anti-GBM glomerulonephritis. Inclusion of both the EDA and EDB regions was associated with glomerular TGFbeta expression. In contrast, in mice with Th2-mediated graft-versus-host disease, a model for lupus nephritis, the FN transcripts included neither the EDA nor the EDB region, and renal TGFbeta expression was absent. Compared to normal MCs in culture, MCs transfected with IL-4 produced lower amounts of FN and demonstrated less EDA inclusion, while MC that had been treated with TGFbeta showed increased production of FN and more EDA inclusion. Renal biopsies from patients with renal diseases, except those taken from patients with lupus nephritis, showed higher TGFbeta levels, higher FN levels, and more EDA inclusion than controls. TGFbeta may be a key player in the development of GS by inducing local FN production and alternative splicing of FN mRNA. In lupus glomerulonephritis, in which the involvement of TGFbeta in GS is less prominent, Th2 cytokines such as IL-4 probably account for increased intrarenal collagen synthesis and subsequent FN accumulation from the circulation. In conclusion, neither alternative FN splicing, nor a high transcription level of TGFbeta, appears to be a general prerequisite for the development of GS.

Alternative Splicing↗

PubMed1990

Localization during development of alternatively spliced forms of cytotactin mRNA by in situ hybridization.

Cytotactin, an extracellular glycoprotein found in neural and nonneural tissues, influences a variety of cellular phenomena, particularly cell adhesion and cell migration. Northern and Western blot analysis and in situ hybridization were used to determine localization of alternatively spliced forms of cytotactin in neural and nonneural tissues using a probe (CT) that detected all forms of cytotactin mRNA, and one (VbVc) that detected two of the differentially spliced repeats homologous to the type III repeats of fibronectin. In the brain, the levels of mRNA and protein increased from E8 through E15 and then gradually decreased until they were barely detectable by P3. Among the three cytotactin mRNAs (7.2, 6.6, and 6.4 kb) detected in the brain, the VbVc probe hybridized only to the 7.2-kb message. In isolated cerebella, the 220-kD polypeptide and 7.2-kb mRNA were the only cytotactin species present at hatching, indicating that the 220-kD polypeptide is encoded by the 7.2-kb message that contains the VbVc alternatively spliced insert. In situ hybridization showed cytotactin mRNA in glia and glial precursors in the ventricular zone throughout the central nervous system. In all regions of the nervous system, cytotactin mRNAs were more transient and more localized than the polypeptides. For example, in the radial glia, cytotactin mRNA was observed in the soma whereas the protein was present externally along the glial fibers. In the telencephalon, cytotactin mRNAs were found in a narrow band at the edge of a larger region in which the protein was wide-spread. Hybridization with the VbVc probe generally overlapped that of the CT probe in the spinal cord and cerebellum, consistent with the results of Northern blot analysis. In contrast, in the outermost tectal layers, differential hybridization was observed with the two probes. In nonneural tissues, hybridization with the CT probe, but not the VbVc probe, was detected in chondroblasts, tendinous tissues, and certain mesenchymal cells in the lung. In contrast, hybridization with both probes was observed in smooth muscle and lung epithelium. Both epithelium and mesenchyme expressed cytotactin mRNA in varying combinations: in the choroid plexus, only epithelial cells expressed cytotactin mRNA; in kidney, only mesenchymal cells; and in the lung, both of these cell types contained cytotactin mRNA. These spatiotemporal changes during development suggest that the synthesis of the various alternatively spliced cytotactin mRNAs is responsive to tissue-specific local signals and prompt a search for functional differences in the various molecular forms of the protein.

Animals↗

PubMed1997

Detection of opioid receptor mRNA by RT-PCR reveals alternative splicing for the delta- and kappa-opioid receptors.

The three mu-, delta- and kappa-opioid receptors have recently been cloned and characterized at the molecular level. Our analysis of opioid receptor transcripts by RT-PCR revealed two PCR products derived from delta and kappa mRNAs with size higher than expected from the known cDNA sequences. DNA sequencing showed additional nucleotides inserted between the known splice sites, indicating the possible existence of alternative splicing pathways for delta and kappa receptors. The novel delta-opioid receptor transcript is expressed in mouse brain and contains a 243 bp insertion. This additional sequence is located at the splice junction between the first and second coding exons and is encoded by a single exon located 9 kb upstream exon 2 in the mDOR gene. The other alternative transcript occurs in human monocytic and T lymphocytic cell lines and encodes a novel form of the kappa-opioid receptor. The PCR product presents a 23 bp deletion at the 3' end of exon 2 followed by a 246 bp insertion found between exons 2 and 3. In the hKOR gene, this insertion is encoded by two DNA segments. One of them is located 0.4 kb downstream exon 2 while the second is flanking exon 3 on the 5' side. Both novel putative delta and kappa exons present in-frame stop codons that would lead to truncated receptor proteins. A possible functional or regulatory role of these shorter proteins in opioid function remains to be determined.

Alternative Splicing↗

PubMed2000

The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation.

Individual members of the serine-arginine (SR) and heterogeneous nuclear ribonucleoprotein (hnRNP) A/B families of proteins have antagonistic effects in regulating alternative splicing. Although hnRNP A1 accumulates predominantly in the nucleus, it shuttles continuously between the nucleus and the cytoplasm. Some but not all SR proteins also undergo nucleo-cytoplasmic shuttling, which is affected by phosphorylation of their serine/arginine (RS)-rich domain. The signaling mechanisms that control the subcellular localization of these proteins are unknown. We show that exposure of NIH-3T3 and SV-40 transformed green monkey kidney (COS) cells to stress stimuli such as osmotic shock or UVC irradiation, but not to mitogenic activators such as PDGF or EGF, results in a marked cytoplasmic accumulation of hnRNP A1, concomitant with an increase in its phosphorylation. These effects are mediated by the MKK(3/6)-p38 pathway, and moreover, p38 activation is necessary and sufficient for the induction of hnRNP A1 cytoplasmic accumulation. The stress-induced increase in the cytoplasmic levels of hnRNP A/B proteins and the concomitant decrease in their nuclear abundance are paralleled by changes in the alternative splicing pattern of an adenovirus E1A pre-mRNA splicing reporter. These results suggest the intriguing possibility that signaling mechanisms regulate pre-mRNA splicing in vivo by influencing the subcellular distribution of splicing factors.

3T3 Cells↗

PubMed2000

Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors.

CD45 is a transmembrane glycoprotein possessing tyrosine phosphatase activity, which is involved in cell signaling. CD45 is expressed on the surface of most leukocytes and can be alternatively spliced by the inclusion or skipping of three variable exons (4, 5, and 6 or A, B, and C) to produce up to eight isoforms. In T cells, the splicing pattern of CD45 isoforms changes after activation; naive cells express high m.w. isoforms of CD45 which predominantly express exon A (CD45RA), whereas activated cells lose expression of exon A to form low m.w. isoforms of CD45 including CD45RO. Little is known about the specific factors controlling the switch in CD45 splicing which occurs on activation. In this study, we examined the influence of the SR family of splicing factors, which, like CD45, are expressed in tissue-specific patterns and have been shown to modulate the alternative splicing of a variety of transcripts. We show that specific SR proteins have antagonistic effects on CD45 splicing, leading either to exon inclusion or skipping. Furthermore, we were able to demonstrate specific changes in the SR protein expression pattern during T cell activation.

Alternative Splicing↗