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Results for “Spliceosomes”

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At least 703 records · Page 39Linked to original sources

PubMed2003

Inhibition of pre-mRNA splicing by cisplatin and platinum analogs.

Our previous study demonstrated that the anticancer agent cis-diamminedichloroplatinum (II) (cis-DDP) inhibited the self-splicing activity of the Tetrahymena rRNA. The present study investigated the effects of cis-DDP on pre-mRNA splicing using a HeLa cell nuclear extract. A 2-h exposure of cis-DDP inhibited the splicing of the human B-globin pre-mRNA in a concentration-dependent manner. The concentration required for 50% inhibition of splicing (IC50) was 51 microM. Complete inhibition of spliceosome assembly occurred when the extracts were incubated with 150 microM cis-DDP. The inhibition of splicing by cis-DDP occurred at early events during spliceosome formation and to a greater extent if the extract was pre-incubated with cis-DDP in the absence of pre-mRNA. Splicing was inhibited when both pre-mRNA and cis-DDP were added simultaneously to the reaction mixture but not when cis-DDP was added 30 min after splicing was initiated with pre-mRNA. Clinically useful platinum analogs (ormaplatin, carboplatin, cis-tetraplatin and iproplatin) as well as the clinically ineffective Pt(dien)C1+, compound were tested for their ability to inhibit pre-mRNA splicing. The Pt(dien)C1+ compound, which acts in a monofunctional manner only, failed to inhibit splicing. A varying degree of splicing inhibition was observed for the other platinum analogs studied; the inhibitory activity decreased in the following order: ormaplatin > cis-tetraplatin > cis-DDP > iproplatin > carboplatin. We describe a novel mechanism that may be involved in the activity and/or toxicity of platinum agents.

Antineoplastic Agents↗

PubMed1993

Characterization of the interchromatin region as the nuclear domain containing snRNPs in plant cells. A cytochemical and immunoelectron microscopy study.

The combination of electron microscopy (EM) cytochemical with immunocytochemical methods is used to characterize the interchromatin region (IR) of the plant cell nucleus. Cryoprocessing of the sample provides a better ultrastructural preservation and allows the observation of some differences in the fine structure of the IR which shows a denser aspect resulting from the lower extraction of components with low-temperature methods. A complex network of fibrillar structures and isolated or clustered 30 to 50-nm granules are observed in the IR. Anti-DNA antibodies combined with the NAMA-Ur method for DNA or the EDTA staining, preferential for RNPs, allow the detection of chromatin fibers in the IR. Bismuth staining reveals the presence of highly phosphorylated proteins in some interchromatin structures. The spliceosomal snRNPs are immunolocalized on cryosections and Lowicryl sections of plant cells using monoclonal and polyclonal antibodies. They provide a homogeneous immunofluorescence pattern with no speckles. This is in correlation with the labeling at EM, immunogold particles decorate the EDTA-positive fibrillar structures of the IR but no labeling is found over the 30 to 50-nm granules. The presence of the spliceosomal snRNPs, DNA and phosphorylated proteins in the IR indicate that this nuclear domain plays a major role in pre-messenger RNA splicing and, possibly in transcription, in the plant cell nucleus.

Allium↗

PubMed1993

A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing.

The polypyrimidine (py) tract of introns is required for efficient spliceosome assembly and splicing of pre-mRNAs. A detailed mutational analysis of the py tract of an adenovirus 2 intron was carried out. Utilizing a "precursor in pieces" vector system, it was possible to synthesize py tract mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs were analyzed for in vitro splicing, for formation of splicing complexes, and for binding to proteins in the HeLa nuclear extract. Chimeric pre-mRNAs that contained the yeast branch point consensus sequence (UAC-UAAC) and altered py tracts were also analyzed. Mutational analysis showed the following. First, any mutation in the py tract that affected splicing did so by interferring with complex A formation in spliceosome assembly. Second, introduction of purines into the py tract is detrimental only if the length of the tract is shortened and if there is a reduction in the number of consecutive uracil residues. Third, uracil and cytosine do not have equivalent functions in the py tract. Our results with chimeric pre-mRNAs also show that a strong py tract can partially replace a weak branch point sequence and a strong branch point sequence can partially replace a weak py tract. Finally, the one surprising finding obtained when examining protein binding was that a mutant pre-mRNA did not bind to heterogeneous nuclear ribonucleoprotein C proteins and yet spliced close to wild type level.

Adenoviruses, Human↗

PubMed1995

Anchorage of adenoviral RNAs to clusters of interchromatin granules.

Previous in situ hybridization experiments have revealed that clusters of interchromatin granules in adenovirus type 5 infected HeLa cells contain not only spliceosome components but also significant amounts of viral RNA and poly(A)+ RNA molecules whereas nonpolyadenylated viral RNA molecules are present within the still enigmatic viral compact rings. To determine the levels of association of the viral RNA molecules with cellular clusters of interchromatin granules and viral compact rings, we investigated the effects of a cell extraction technique on these structures. The spreading apart of the nucleoproteins by exposure of infected cells to a detergent-containing hypotonic solution, which exclusively preserves structurally linked components, resulted in the persistence within the clusters of interchromatin granules of U1 snRNA, U2 snRNA, viral RNA, and poly(A)+ RNA. These data clearly reveal that, in addition to the well-known strong binding of spliceosome components within the clusters of interchromatin granules, there also is an anchorage of viral RNA and messenger RNA molecules to these structures, which suggests functional relationships. Taken together, the data indicate that the clusters of interchromatin granules might be the sites of accumulation and retention of those cell and viral messenger RNA molecules that are transiently stored in the nucleus before their degradation or their transport to the cytoplasm. In addition, the firm binding of nonpolyadenylated viral RNA to the viral compact rings suggests a role for these structures in the transient storage of the nonused portions of the viral primary late transcripts.

Adenoviruses, Human↗

PubMed1997

The [U4/U6.U5] tri-snRNP-specific 27K protein is a novel SR protein that can be phosphorylated by the snRNP-associated protein kinase.

SR proteins play important roles in the recognition and selection of the 3' and 5' splice site of a given intron and contribute to the phosphorylation/dephosphorylation-mediated regulation of pre-mRNA splicing. Recent studies have demonstrated that the U1 snRNP is recruited to the 5' splice site by protein/protein interactions involving the SR domains of the U1-70K protein and SF2/ASF. Recently, it was suggested that SR proteins might also contribute to the binding of the [U4/U6.U5] tri-snRNP to the pre-spliceosome (Roscigno RF, Garcia-Blanco MA, 1995, RNA 1:692-706), although it remains unclear whether these SR proteins interact with proteins of the tri-snRNP complex. As a first step toward the identification of proteins that could potentially mediate the integration of the [U4/U6.U5] tri-snRNP complex into the spliceosome, we investigated whether purified [U4/U6.U5] tri-snRNP complexes contain SR proteins. Three proteins in the tri-snRNP complex with approximate molecular weights of 27, 60, and 100 kDa were phosphorylated by purified snRNP-associated protein kinase, which has been shown previously to phosphorylate the serine/ arginine-rich domains of U1-70K and SF2/ASF (Woppmann A et al., 1993, Nucleic Acids Res 21:2815-2822). These proteins are thus prime candidates for novel tri-snRNP SR proteins. Here, we describe the biochemical and molecular characterization of the 27K protein. Analysis of a cDNA encoding the 27K protein revealed an N-terminal SR domain strongly homologous (54% identity) to the SR domain of the U1 snRNP-specific 70K protein. In contrast to many other SR proteins, the 27K protein does not contain an RNA-binding domain. The 27K protein can be phosphorylated in vitro by the snRNP-associated protein kinase and exhibits several isoelectric variants upon 2D gel electrophoresis. Thus, the tri-snRNP-specific 27K protein could potentially be involved in SR protein-mediated protein/protein interactions and, additionally, its phosphorylation state could modulate pre-mRNA splicing.

Amino Acid Sequence↗

PubMed1997

Identification of a new coiled body component.

Coiled bodies are small, round nuclear inclusions that have been identified in many somatic cell types. Equivalent structures are found in the germinal vesicles of amphibian and insect oocytes, known respectively as sphere organelles and Binnenkörper. Their functions are not known, but their molecular composition is being brought to light. In addition to the nucleolar protein, fibrillarin, coiled bodies contain DNA topoisomerase I and an array of RNA processing molecules characteristic of spliceosomes. One coiled body protein absent from nucleoli and spliceosomes, known as p80-coilin, has also been described. We have now identified pigpen, a new member of the EWS family of proteins, as a second protein enriched in coiled bodies. In an earlier report we found that pigpen's structure and expression pattern were suggestive of a role in endothelial cell proliferation and differentiation. In this brief report we characterize pigpen's nuclear compartment and describe its reorganization during mitosis.

Animals↗

PubMed2026

Clonal Hematopoiesis and Incident Heart Failure.

IMPORTANCE: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with acquired preleukemic variants, has been associated with cardiometabolic diseases, including heart failure (HF). However, prior studies have lacked power to examine less common CHIP driver variants and have not investigated potential mediators of the CHIP-HF association. OBJECTIVE: To test whether specific CHIP subtypes are associated with incident HF and determine the extent to which CHIP-associated comorbidities mediate this association. DESIGN, SETTING, AND PARTICIPANTS: This was a UK Biobank prospective population-based cohort study of community-dwelling adults in the UK, with enrollment from 2006 to 2010 and follow-up through 2020. Included were participants with whole-exome sequencing (WES) and without prevalent HF, hematologic malignancy, or other CHIP-associated comorbidities (coronary artery disease [CAD], atrial fibrillation [AF], type 2 diabetes [T2D], or chronic kidney disease [CKD]) at baseline. Study data were analyzed from April through October 2025. EXPOSURES: Presence of CHIP and gene-specific CHIP subtypes (DNMT3A, non-DNMT3A, TET2, ASXL1, JAK2, DNA damage repair genes, and spliceosome genes). Mediation analyses examined CHIP-associated comorbidities (CAD, AF, T2D, and CKD). MAIN OUTCOMES AND MEASURES: The primary outcome was incident HF. Cox regression tested associations of CHIP and CHIP subtypes with incident HF, adjusted for age, sex, race, and cardiovascular risk factors. RESULTS: Among 417 616 participants (mean [SD] age, 56.1 [8.1] years; 234 868 female [56.2%]), 7183 (1.7%) developed incident HF over a median (IQR) of 11.1 (10.4-11.8) years of follow-up. CHIP was associated with HF risk (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.15-1.40; P < .001), driven by non-DNMT3A subtypes (aHR, 1.52; 95% CI, 1.33-1.75; P < .001), including associations with TET2, ASXL1, JAK2, and spliceosome CHIP. DNMT3A CHIP was more modestly associated with HF (aHR, 1.15; 95% CI, 1.00-1.31; P = .04). In mediation analyses, development of CAD, AF, T2D, and/or CKD collectively accounted for 28.2% of the association (95% CI, 11.6%-45.4%; P = .001) between non-DNMT3A CHIP and HF. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that CHIP, especially non-DNMT3A CHIP, was associated with incident HF. Other CHIP-associated comorbidities explained only a minority of the association between non-DNMT3A CHIP and HF. These findings suggest that CHIP is an HF risk factor and potential therapeutic target.

Adult↗

PubMed2000

Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins.

A set of seven structurally related Sm proteins forms the core of the snRNP particles containing the spliceosomal U1, U2, U4 and U5 snRNAs. A search of the genomic sequence of Saccharomyces cerevisiae has identified a number of open reading frames that potentially encode structurally similar proteins termed Lsm (Like Sm) proteins. With the aim of analysing all possible interactions between the Lsm proteins and any protein encoded in the yeast genome, we performed exhaustive and iterative genomic two-hybrid screens, starting with the Lsm proteins as baits. Indeed, extensive interactions amongst eight Lsm proteins were found that suggest the existence of a Lsm complex or complexes. These Lsm interactions apparently involve the conserved Sm domain that also mediates interactions between the Sm proteins. The screens also reveal functionally significant interactions with splicing factors, in particular with Prp4 and Prp24, compatible with genetic studies and with the reported association of Lsm proteins with spliceosomal U6 and U4/U6 particles. In addition, interactions with proteins involved in mRNA turnover, such as Mrt1, Dcp1, Dcp2 and Xrn1, point to roles for Lsm complexes in distinct RNA metabolic processes, that are confirmed in independent functional studies. These results provide compelling evidence that two-hybrid screens yield functionally meaningful information about protein-protein interactions and can suggest functions for uncharacterized proteins, especially when they are performed on a genome-wide scale.

Fungal Proteins↗

PubMed2026

Dysregulation of U12-Type Splicing in Lupus Neutrophils.

OBJECTIVE: Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low-density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing. METHODS: LDGs and normal-density granulocytes (NDGs) were isolated from patients with SLE and healthy controls (HCs). CYBA (p22phox) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA-seq) and rMATS software were used to assess alternative splicing, particularly of U12-type intron-containing genes. RESULTS: CYBA expression was reduced in SLE LDGs (n = 11) compared to SLE and HC NDGs (n = 6), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n = 7 SLE, n = 12 HC). CYBA is a U12 intron-containing gene, and transcriptomic analysis revealed broad down-regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12-type intron retention and widespread splicing defects-including exon skipping and mutually exclusive exon use-in genes such as GBP5, MAEA, and STX10. These abnormalities were validated in an independent long-read RNA-seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles. CONCLUSION: Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.

Humans↗

PubMed2001

Multifunctional regulatory proteins that control gene expression in both the nucleus and the cytoplasm.

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre-messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript- and cell-type-specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA- and DNA-binding proteins that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y-box proteins) regulates both transcription and translation whereas another class (e.g., Sex-lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense-mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments.

Animals↗

PubMed2007

Solution structure of domain 6 from a self-splicing group II intron ribozyme: a Mg(2+) binding site is located close to the stacked branch adenosine.

Group II intron self-splicing is essential for the correct expression of organellar genes in plants, fungi, and yeast, as well as of bacterial genes. Self-excision of these autocatalytic introns from the primary RNA transcript is achieved in a two-step mechanism that is apparently analogous to that of the eukaryotic spliceosome. The 2'-OH of a conserved adenosine (the branch point) located within domain 6 (D6) acts as the nucleophile in the first step of splicing. Despite the biological importance of group II introns, little is known about their structural organization and usage of metal ions in catalysis. Here we report the first solution structure of a catalytically active D6 construct encompassing the branch point and the neighboring helical regions from the mitochondrial yeast intron ai5gamma. The branch adenosine is the single unpaired nucleotide, and, in contrast to the spliceosomal branch site, resides within the helix, being partially stacked between two flanking GU wobble pairs. We identified a novel prominent Mg(2+) binding site in the major groove of the branch site. Importantly, Mg(2+) addition does not impair the stacking of the branch adenosine, rather it strengthens the interaction with the flanking uridines, as shown by NMR and fluorescence studies. This means that domain 6 presents the branch adenosine in a stacked fashion to the core of group II introns upon folding to the active conformation.

Adenosine↗

PubMed2005

Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy.

The autosomal recessive spinal muscular atrophy (SMA), a neuromuscular disease and frequent cause of early death in childhood, is caused in 96% of patients by homozygous absence of the survival motor neuron gene (SMN1). The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. A comprehensive molecular genetic analysis of 34 SMA patients who carry one SMN1 gene is presented, including 18 that were previously published. Haplotype analysis with the microsatellite markers Ag1-CA and C212 in these SMA families turned out to be a reliable accessory method in predicting known SMN1 mutations in SMA patients carrying one SMN1 copy. Five novel missense mutations were identified that are localized in: exon 2a c.88G>A (p.D30N) and c.131A>T (p.D44V); exon 3 c.283G>C (p.G95R) and c.332C>G (p.A111G); and exon 6 c.784A>G (p.S262G), respectively. The survival motor neuron (SMN) protein has been shown to be a component of a large complex (termed the SMN complex) that promotes the formation of spliceosomal U small nuclear ribonucleoproteins (snRNPs). Within this complex, SMN forms oligomers and directly interacts via its N-terminus with SMN-interacting protein 1 (SIP1) and via its central Tudor domain with spliceosomal (Sm) proteins. We performed in vitro interaction studies to test whether SMA-causing missense mutations identified in this study interfere with the reported interactions of SMN. Our results show that mutations p.G95R and p.A111G reduce SMN binding to Sm proteins, further confirming the previous finding that the Tudor domain is the essential binding site of SMN to Sm-proteins. However, all mutations, including those in exon 2a, a region shown to be important for the binding of SMN to SIP1, do not disturb the interaction of SMN to SIP1.

Adolescent↗

PubMed1989

Mapping U2 snRNP--pre-mRNA interactions using biotinylated oligonucleotides made of 2'-OMe RNA.

Biotinylated 2'-OMe RNA oligonucleotides complementary to two separate regions of human U2 snRNA have been used as affinity probes to study U2 snRNP--pre-mRNA interactions. Both oligonucleotides bind specifically and allow highly selective removal of U2 snRNP from HeLa cell nuclear extracts. Pre-mRNA substrates can also be specifically affinity selected through oligonucleotides binding to U2 snRNP particles in splicing complexes. Stable binding of U2 snRNP to pre-mRNA is blocked by the pre-binding of an oligonucleotide to the branch site complementary region of U2 snRNA, but not by an oligonucleotide binding to the 5' terminus of U2. Both oligonucleotides affinity select the intron product, but not the intron intermediate, when added after spliceosome assembly has taken place. The effect of 2'-OMe RNA oligonucleotides on splicing complex formation has been used to demonstrate that complexes containing U2 snRNP and unspliced pre-mRNA are precursors to functional spliceosomes.

Base Sequence↗

PubMed1991

In vivo detection of snRNP-rich organelles in the nuclei of mammalian cells.

The in vivo distribution of snRNPs has been analysed by microinjecting fluorochrome-labelled antisense probes into the nuclei of live HeLa and 3T3 cells. Probes for U2 and U5 snRNAs specifically label the same discrete nuclear foci while a probe for U1 snRNA shows widespread nucleoplasmic labelling, excluding nucleoli, in addition to labelling foci. A probe for U3 snRNA specifically labels nucleoli. These in vivo data confirm that mammalian cells have nuclear foci which contain spliceosomal snRNPs. Co-localization studies, both in vivo and in situ, demonstrate that the spliceosomal snRNAs are present in the same nuclear foci. These foci are also stained by antibodies which recognize snRNP proteins, m3G-cap structures and the splicing factor U2AF but are not stained by anti-SC-35 or anti-La antibodies. U1 snRNP and the splicing factor U2AF closely co-localize in the nucleus, both before and after actinomycin D treatment, suggesting that they may both be part of the same complex in vivo.

Animals↗

PubMed1991

The yeast branchpoint sequence is not required for the formation of a stable U1 snRNA-pre-mRNA complex and is recognized in the absence of U2 snRNA.

Commitment complexes contain U1 snRNP as well as pre-mRNA and are the earliest functional complexes that have been described during in vitro spliceosome assembly. We have used a gel retardation assay to analyze the role of the yeast pre-mRNA cis-acting sequences in commitment complex formation. The results suggest that only a proper 5' splice site sequence is required for efficient U1 snRNA-pre-mRNA complex formation. A role for the highly conserved UACUAAC branchpoint sequence is indicated, however, by competition experiments and by the direct analysis of branchpoint mutant substrates, which cannot form one of the two commitment complex species observed with wild-type substrates. The results suggest that the formation of a U1 snRNP-pre-mRNA complex is not dependent upon the presence of a branchpoint sequence but that the branchpoint sequence is recognized prior to U2 snRNP addition during in vitro spliceosome assembly.

Actins↗

PubMed1994

A functional interaction between Rev and yeast pre-mRNA is related to splicing complex formation.

The HIV-1 Rev protein regulates viral gene expression by enhancing the export of partially spliced or nonspliced viral transcripts to the cytoplasm. This activity is mediated by the interaction of Rev with a highly structured viral RNA sequence, the Rev response element (RRE). In this paper, Rev regulation has been recapitulated in the yeast Saccharomyces cerevisiae. The data show that Rev enhances yeast pre-mRNA translation in an RRE-dependent manner and requires intact RNA binding and effector domains. In addition, reporter gene mutations in the 5' splice site and in the branch point are epistatic to and eliminate Rev responsiveness, i.e. some spliceosome assembly pathway steps precede a functional interaction with Rev. The results indicate that some of the Rev-interacting components are conserved between yeast and mammals and suggest that Rev acts on yeast pre-mRNA in the context of the spliceosome.

Biological Transport↗

PubMed1995

Effects of secondary structure on pre-mRNA splicing: hairpins sequestering the 5' but not the 3' splice site inhibit intron processing in Nicotiana plumbaginifolia.

We have performed a systematic study of the effect of artificial hairpins on pre-mRNA splicing in protoplasts of a dicot plant, Nicotiana plumbaginifolia. Hairpins with a potential to form 18 or 24 bp stems strongly inhibit splicing when they sequester the 5' splice site or are placed in the middle of short introns. However, similar 24 bp hairpins sequestering the 3' splice site do not prevent this site from being used as an acceptor. Utilization of the stem-located 3' site requires that the base of the stem is separated from the upstream 5' splice site by a minimum of approximately 45 nucleotides and that another 'helper' 3' splice site is present downstream of the stem. The results indicate that the spliceosome or factors associated with it may have a potential to unfold secondary structure present in the downstream portion of the intron, prior to or at the step of the 3' splice site selection. The finding that the helper 3' site is required for utilization of the stem-located acceptor confirms and extends previous observations, obtained with HeLa cell in vitro splicing systems, indicating that the 3' splice site may be recognized at least twice during spliceosome assembly.

Base Sequence↗

PubMed1995

Sm and Sm-like proteins belong to a large family: identification of proteins of the U6 as well as the U1, U2, U4 and U5 snRNPs.

Several small nuclear RNAs (snRNAs), including the spliceosomal U1, U2, U4 and U5 snRNAs, are associated with Sm proteins. These eight small proteins form a heteromeric complex that binds to snRNAs and plays a major role in small nuclear ribonucleoprotein (snRNP) biogenesis and transport. These proteins are also a major target for autoantibodies in the human disease systemic lupus erythematosus. By sequence comparison I have shown that all the known Sm proteins share a common structural motif which might explain their immunological cross-reactivity. Database searches using this motif uncovered a large number of Sm-like proteins from plants, animals and fungi. These proteins have been grouped in at least 13 different subfamilies. Genes encoding divergent yeast members were cloned and used to produce tagged fusion proteins. Some of these proteins are canonical Sm proteins as they associate with the yeast U1, U2, U4/U6 and U5 snRNAs. Surprisingly, one Sm-like protein was found to be a component of the U6 snRNP. These findings have implications for the structure of the Sm protein complex, spliceosomal snRNP evolution, snRNA transport and modification as well as the involvement of Sm proteins in systemic lupus erythematosus.

Amino Acid Sequence↗