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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterocyst-forming cyanobacteria have multiple genes encoding proteins that are similar to the RNP family of eukaryotic RNA-binding proteins. Three genes from two strains of cyanobacteria (Anabaena and Chlorogloeopsis) have been sequenced. All three putative gene products contain a single RNA Recognition Motif (RRM) that includes the highly conserved RNP1 and RNP2 regions and all three have an auxiliary motif consisting either of a short glycine-rich carboxy-terminal tail or a carboxy-terminal tail rich in both asparagine and glycine. RNA-binding protein genes are abundant in heterocyst-forming filamentous cyanobacteria but are not abundant in non-heterocyst-forming filamentous or unicellular cyanobacteria suggesting that the cyanobacterial proteins may play a role in gene expression during heterocyst differentiation. The cyanobacterial gene products share a significant degree of similarity with the RNP family of RNA-binding proteins which includes snRNP proteins, hnRNP proteins, nucleolins, as well as some regulatory proteins and some plant chloroplast proteins. Although the exact function of the cyanobacterial gene products is not yet known, their similarity to eukaryotic proteins suggests that they may play a role in RNA processing and metabolism. Finally, the presence of these genes in cyanobacteria has implications for the evolution of RNA binding proteins and RNA processing.
J Mol Biol 1994 Jan 21
PMID:Heterocyst-forming filamentous cyanobacteria encode proteins that resemble eukaryotic RNA-binding proteins of the RNP family. 828 20

Small nuclear (sn) ribonucleoprotein (RNP) U2 functions in the splicing of mRNA by recognizing the branch site of the unspliced pre-mRNA. When HeLa nuclear splicing extracts are centrifuged on glycerol gradients, U2 snRNPs sediment at either 12S (under high salt concentration conditions) or 17S (under low salt concentration conditions). We isolated the 17S U2 snRNPs from splicing extracts under nondenaturing conditions by using centrifugation and immunoaffinity chromatography and examined their structure by electron microscope. In addition to common proteins B', B, D1, D2, D3, E, F, and G and U2-specific proteins A' and B", which are present in the 12S U2 snRNP, at least nine previously unidentified proteins with apparent molecular masses of 35, 53, 60, 66, 92, 110, 120, 150, and 160 kDa bound to the 17S U2 snRNP. The latter proteins dissociate from the U2 snRNP at salt concentrations above 200 mM, yielding the 12S U2 snRNP particle. Under the electron microscope, the 17S U2 snRNPs exhibited a bipartite appearance, with two main globular domains connected by a short filamentous structure that is sensitive to RNase. These findings suggest that the additional globular domain, which is absent from 12S U2 snRNPs, contains some of the 17S U2-specific proteins. The 5' end of the RNA in the U2 snRNP is more exposed for reaction with RNase H and with chemical probes when the U2 snRNP is in the 17S form than when it is in the 12S form. Removal of the 5' end of this RNA reduces the snRNP's Svedberg value from 17S to 12S. Along with the peculiar morphology of the 17S snRNP, these data indicate that most of the 17S U2-specific proteins are bound to the 5' half of the U2 snRNA.
Mol Cell Biol 1993 Jan
PMID:Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. 838 Feb 23

Mammalian U6 small nuclear RNA (snRNA) is heterogeneous with respect to the number of 3' terminal U residues. The major form terminates with five U residues and a 2',3' cyclic phosphate. Because of the presence in HeLa cell nuclear extracts of a terminal uridylyl transferase, a minor form of U6 snRNA is elongated, producing multiple species containing up to 12 U residues. In this study we have used glycerol gradients to demonstrate that these U6 snRNA forms are assembled into U6 ribonucleoprotein (RNP), U4/U6 snRNPs, and U4/U5/U6 tri-snRNP complexes. Furthermore, glycerol gradients combined with affinity selection of biotinylated pre-mRNAs led us to show that elongated forms of U6 snRNAs enter the spliceosome and that some of these become shortened with time to a single species having the same characteristics as the major form of U6 snRNA present in mammalian nuclear extracts. We propose that this elongation-shortening process is related to the function of U6 snRNA in mammalian pre-mRNA splicing.
Mol Cell Biol 1993 Mar
PMID:Mammalian U6 small nuclear RNA undergoes 3' end modifications within the spliceosome. 844 2

5'-end maturation of messenger RNAs via acquisition of a trans-spliced leader sequence occurs in several primitive eukaryotes, some of which are parasitic. This type of trans-splicing proceeds though a two-step reaction pathway directly analogous to that of cis-splicing and like cis-splicing it requires multiple U snRNP cofactors. This minireview attempts to provide a brief synopsis of our current understanding of the evolution and biological significance of trans-splicing. Progress in deciphering the mechanism of trans-splicing, particularly as it relates to current models of cis-splicing, is also discussed.
Mol Biochem Parasitol 1995 Jul
PMID:trans-splicing: an update. 857 17

The temperature-sensitive prp24-1 mutation defines a gene product required for the first step in pre-mRNA splicing. PRP24 is probably a component of the U6 snRNP particle. We have applied genetic reversion analysis to identify proteins that interact with PRP24. Spontaneous revertants of the temperature-sensitive (ts)prp24-1 phenotype were analyzed for those that are due to extragenic suppression. We then extended our analysis to screen for suppressors that confer a distinct conditional phenotype. We have identified a temperature-sensitive extragenic suppressor, which was shown by genetic complementation analysis to be allelic to prp21-1. This suppressor, prp21-2, accumulates pre-mRNA at the non-permissive temperature, a phenotype similar to that of prp21-1. prp21-2 completely suppresses the splicing defect and restores in vivo levels of the U6 snRNA in the prp24-1 strain. Genetic analysis of the suppressor showed that prp21-2 is not a bypass suppressor of prp24-1. The suppression of prp24-1 by prp21-2 is gene specific and also allele specific with respect to both the loci. Genetic interactions with other components of the pre-spliceosome have also been studied. Our results indicate an interaction between PRP21, a component of the U2 snRNP, and PRP24, a component of the U6 snRNP. These results substantiate other data showing U2-U6 snRNA interactions.
Mol Gen Genet 1996 Feb 25
PMID:An extragenic suppressor of prp24-1 defines genetic interaction between PRP24 and PRP21 gene products of Saccharomyces cerevisiae. 860 41

Nucleolin is an abundant nucleolar protein, which plays an essential, but largely unknown role in ribosome biogenesis. Nucleolin contains four consensus RNA-binding domains (CS-RBD), the presence of which suggests that the molecular function of this protein is likely reflected by its RNA-binding properties. Indeed, by immunocytological analysis performed on ribosomal transcription units, we have found several nucleolin molecules associated with nascent pre-rRNA. In mouse, two high-affinity binding sites with an apparent dissociation constant (Kd) of 50 to 100 nM have been mapped in the 5' ETS upstream from the early pre-rRNA processing site. Interestingly, nucleolin of mouse origin has recognized analogous sequences in the 5' ETS of human pre-rRNA. In parallel, selection-amplification (SELEX) experiments have identified an 18-nucleotide long RNA sequence that binds nucleolin with high affinity (Kd 5 to 20 nM) and shares a common UCCCGA motif with the characterized pre-rRNA binding sites. By mutagenesis and a structural analysis, we have characterized the nucleolin RNA binding site and found that it is constituted by a minimal 18-nucleotide long stem-loop structure. The sequence UCCCGA that is found within the hairpin loop is necessary for the specific interaction. Mutation of any of the C or G residues within this motif abolishes nucleolin interaction. Furthermore, point mutation in the stem that completely disrupt the hairpin structure also prevents nucleolin binding. By determining the minimal 5' and 3' ends of the RNA that is bound to the protein we concluded that nucleolin binding site is constituted by a short four to five-base-pair stem and an eight-nucleotide loop. This structural motif is very similar to hairpins recognized by two other CS-RBD-containing proteins (U1 snRNP A and U2 snRNP B"). Possible functional implications of our findings are discussed.
J Mol Biol 1996 Jul 05
PMID:Nucleolin is a sequence-specific RNA-binding protein: characterization of targets on pre-ribosomal RNA. 867 91

U1 RNP C polypeptide is a ubiquitous and highly conserved protein that is found associated to the U1 small nuclear ribonuclear particle (U1 snRNP). The U1 snRNP is involved in pre-mRNA splicing by defining introns and exons and by binding to consensus sequences within the pre-mRNA. In the present study we immunoscreened a mouse testicular phagemid cDNA library with an anti-Sm serum from patients with systemic lupus erythematosus. Sequence analysis of a positive clone containing a 0.75 kb cDNA insert revealed that it encodes the entire amino acid sequence of the U1 RNP C polypeptide. Northern blots of total RNA isolated from testes and various adult mouse tissues demonstrated that the 0.75 kb transcript is highly expressed in the testes and that it begins developmentally at day 18 postpartum, corresponding to the appearance of preleptotene spermatocytes. In situ hybridization confirmed the meiotic and post-meiotic expression of this transcript. LM immunoperoxidase staining with the anti-Sm serum localized spliceosome snRNPs predominantly in the nuclei of somatic and germinal testicular cells but not in elongated spermatids. EM immunogold labeling confirmed the LM observations but additionally showed that snRNP content peaked in the nuclei of pachytene spermatocytes and that 2 cytoplasmic components found exclusively in meiotic and post-meiotic germ cells were intensively reactive. Immunoblots of testicular homogenates probed with the anti-Sm serum revealed several reactive proteins, of which one, a 21 kDa polypeptide, could be the U1 RNP C based on its predicted molecular weight. In summary we report an isoform of U1 RNP C which is testis specific and which may play a role in mRNA splicing exclusively in meiotic and post-meiotic germ cells during spermatogenesis.
Mol Reprod Dev 1997 Apr
PMID:Molecular cloning and developmental expression of a small ribonuclear protein in the mouse testis. 909 92

The association of U2 snRNP with the pre-mRNA branch region is a critical step in the assembly of spliceosomal complexes. We describe an assembly process that reveals both minimal requirements for formation of a U2 snRNP-substrate RNA complex, here designated the Amin complex, and specific interactions with the branch site adenosine. The substrate is a minimal RNA oligonucleotide, containing only a branch sequence and polypyrimidine tract. Interactions at the branch site adenosine and requirements for polypyrimidine tract-binding proteins for the Amin complex are the same as those of authentic prespliceosome complex A. Surprisingly, Amin complex formation does not require U1 snRNP or ATP, suggesting that these factors are not necessary for stable binding of U2 snRNP per se, but rather are necessary for accessibility of components on longer RNA substrates. Furthermore, there is an ATP-dependent activity that releases or destabilizes U2 snRNP from branch sequences. The simplicity of the Amin complex will facilitate a detailed understanding of the assembly of prespliceosomes.
Mol Cell Biol 1997 May
PMID:A minimal spliceosomal complex A recognizes the branch site and polypyrimidine tract. 911 66

Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different proteins which can bind to nascent pre-mRNA. Among these, the hnRNP-A/B proteins form a subgroup of highly related proteins consisting of two adjacent RNA binding domains (RBD) within the N-terminal parts, whereas the C-terminal halves contain almost 50% glycine residues. These proteins, in particular A2/RA33, are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). In SLE anti-hnRNP antibodies frequently occur together with antibodies to U1 small nuclear RNP (U1-snRNP) and Sm, other proteins of the spliceosome. Preliminary epitope mapping studies have revealed major antibody binding sites in the RNA binding regions for all three diseases. Nevertheless, there is some indication of disease specific epitope recognition. Studies in animal models have demonstrated anti-RA33/hnRNP-A/B antibodies in lupus-prone mouse strains. Thus, autoantibodies to the spliceosomal hnRNP-A/B proteins are a common feature of RA, SLE, and MCTD. However, these diseases differ in their reactivities to other spliceosomal proteins, especially anti-U1 snRNP and Sm. Therefore, anti-RA33/hnRNP-A/B autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenesis of rheumatic autoimmune diseases.
Mol Biol Rep 1996
PMID:Clinical and immunological aspects of autoantibodies to RA33/hnRNP-A/B proteins--a link between RA, SLE and MCTD. 911 25

The hnRNP A1 pre-mRNA is alternatively spliced to yield the A1 and A1b mRNAs, which encode proteins differing in their ability to modulate 5' splice site selection. Sequencing a genomic portion of the murine A1 gene revealed that the intron separating exon 7 and the alternative exon 7B is highly conserved between mouse and human. In vitro splicing assays indicate that a conserved element (CE1) from the central portion of the intron shifts selection toward the distal donor site when positioned in between the 5' splice sites of exon 7 and 7B. In vivo, the CE1 element promotes exon 7B skipping. A 17-nucleotide sequence within CE1 (CE1a) is sufficient to activate the distal 5' splice site. RNase T1 protection/immunoprecipitation assays indicate that hnRNP A1 binds to CE1a, which contains the sequence UAGAGU, a close match to the reported optimal A1 binding site, UAGGGU. Replacing CE1a by different oligonucleotides carrying the sequence UAGAGU or UAGGGU maintains the preference for the distal 5' splice site. In contrast, mutations in the AUGAGU sequence activate the proximal 5' splice site. In support of a direct role of the A1-CE1 interaction in 5'-splice-site selection, we observed that the amplitude of the shift correlates with the efficiency of A1 binding. Whereas addition of SR proteins abrogates the effect of CE1, the presence of CE1 does not modify U1 snRNP binding to competing 5' splice sites, as judged by oligonucleotide-targeted RNase H protection assays. Our results suggest that hnRNP A1 modulates splice site selection on its own pre-mRNA without changing the binding of U1 snRNP to competing 5' splice sites.
Mol Cell Biol 1997 Apr
PMID:An intron element modulating 5' splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1. 912 25


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