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Query: UNIPROT:P06889 (Mol)
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The binding of a U1 small nuclear ribonucleoprotein (snRNP) particle to the 5' splice site region of a pre-mRNA is a primary step of intron recognition. In this report, we identify a novel 75-kDa polypeptide of Saccharomyces cerevisiae, Prp39p, necessary for the stable interaction of mRNA precursors with the snRNP components of the pre-mRNA splicing machinery. In vivo, temperature inactivation or metabolic depletion of Prp39p blocks pre-mRNA splicing and causes growth arrest. Analyses of cell extracts reveal a specific and dramatic increase in the electrophoretic mobility of the U1 snRNP particle upon Prp39p depletion and demonstrate that extracts deficient in Prp39p activity are unable to form either the CC1 or CC2 commitment complex band characteristic of productive U1 snRNP/pre-mRNA association. Immunological studies establish that Prp39p is uniquely associated with the U1 snRNP and is recruited with the U1 snRNP into splicing complexes. On the basis of these and related observations, we propose that Prp39p functions, at least in part, prior to stable branch point recognition by the U1 snRNP particle to facilitate or stabilize the U1 snRNP/5' splice site interaction.
Mol Cell Biol 1994 Jun
PMID:Commitment of yeast pre-mRNA to the splicing pathway requires a novel U1 small nuclear ribonucleoprotein polypeptide, Prp39p. 819 8

We have studied the ultrastructural distribution of heterogeneous nuclear ribonucleoproteins (hnRNPs), small nuclear ribonucleoproteins (snRNPs), and ribosomal proteins during mouse spermatogenesis and spermiogenesis by means of specific antibodies and immunocytochemistry. All the above components were detectable from primary spermatocytes until the spermatid elongation phase, when the RNA synthetic activity is known to cease. Ribosomal protein (P1/P2 and L7) labeling disappeared as early as during the acrosome phase, and nucleoli were no longer labeled even during the cap phase. The nucleoplasmic structures labeled with the different anti-nucleoplasmic RNP immunoprobes corresponded, until the acrosome phase, to those previously observed as targets of the same antibodies in the nucleoplasm of somatic cell nuclei. Clusters of interchromatin granules of spermatocyte and early spermatid nuclei exhibit some labeling for hnRNP when compared with nuclei of Sertoli cells or previously analyzed liver or tissue culture cells, where these structural constituents usually remain weakly labeled or unlabeled. In spermatids in step 10, another type of nuclear granule, resembling perichromatin granules, but occurring in aggregates, can be observed. These structural constituents were labeled with antibodies recognizing nucleoplasmic snRNP antigens and therefore suggesting a non-nucleolar origin of these granules. Finally, we have observed nucleoplasmic areas of fibrogranular material, occurring only in primary spermatocytes. These components were labeled with anti-ribosomal protein antibodies but did not contain either hnRNPs or snRNPs.
Mol Reprod Dev 1993 Jul
PMID:Immunoelectron microscope localization of snRNP, hnRNP, and ribosomal proteins in mouse spermatogenesis. 835 31

To examine the stability of yeast (Saccharomyces cerevisiae) pre-mRNA structures, we inserted a series of small sequence elements that generated potential RNA hairpins at the 5' splice site and branch point regions. We analyzed spliceosome assembly and splicing in vitro as well as splicing and nuclear pre-mRNA retention in vivo. Surprisingly, the inhibition of in vivo splicing approximately paralleled that of in vitro splicing. Even a 6-nucleotide hairpin could be shown to inhibit splicing, and a 15-nucleotide hairpin gave rise to almost complete inhibition. The in vitro results indicate that hairpins that sequester the 5' splice site have a major effect on the early steps of spliceosome assembly, including U1 small nuclear ribonucleoprotein binding. The in vivo experiments lead to comparable conclusions as the sequestering hairpins apparently result in the transport of pre-mRNA to the cytoplasm. The observations are compared with previous data from both yeast and mammalian systems and suggest an important effect of pre-mRNA structure on in vivo splicing.
Mol Cell Biol 1993 Nov
PMID:Short artificial hairpins sequester splicing signals and inhibit yeast pre-mRNA splicing. 841 77

The small nuclear ribonucleoprotein particles U1, U2, U4/U6 and U5 participate in the removal of introns from pre-messenger RNAs in the nucleus. Three genes encoding U5snRNAs, the RNA moiety of U5snRNPs, have been isolated from maize. As in other plant UsnRNA gene families the three maize U5snRNA genes exhibit sequence variation. Two of the gene variants (MzU5.1 and MzU5.2) are clearly expressed after transfection into maize leaf protoplasts while the third gene variant (MzU5.3) is expressed at very low levels. These different levels of expression cannot be directly correlated with sequence changes in the highly conserved Upstream Sequence Element (USE) required for expression of Arabidopsis UsnRNA genes nor with differential stability of the U5snRNA transcripts. Further sequence elements may therefore have a role in regulating maize UsnRNA gene expression.
Plant Mol Biol 1993 Jan
PMID:Differential expression of U5snRNA gene variants in maize (Zea mays) protoplasts. 842 43

C-reactive protein (CRP) binds to chromatin, histones, and small nuclear ribonucleoproteins (snRNPs) through a phosphocholine (PC)-inhibitable, calcium-dependent binding site. snRNPs process pre-mRNA to mature mRNA and are composed of small uridine-rich RNAs (designated U1, U2, U5 and U4/U6) and associated proteins. We have shown that CRP binds to snRNPs in intact cells and to the U1 snRNP-specific 70 K protein in cell extracts. To determine whether CRP bound to other snRNP proteins, snRNPs were purified from rabbit thymus extract and CRP binding was assessed by blotting. CRP bound to a protein with the same mobility as Sm-D as well as to the 70 K protein. CRP specifically bound to and precipitated a fusion protein containing full-length Sm-D, confirming the binding of CRP to Sm-D. Binding was inhibited by PC and by EDTA. Binding studies using deletion mutants of the Sm-D fusion protein revealed that CRP binding was mediated by the C-terminal region of Sm-D, a region which binds autoantibodies and is proposed to bind to RNA. A comparison of the peptide regions on different autoantigens suggests that there is a shared motif to which CRP binds.
Mol Immunol 1993 Jun
PMID:C-reactive protein (CRP) binding to the Sm-D protein of snRNPS. Identification of a short polypeptide binding region. 850 40

The SmN protein is a component of small nuclear ribonucleoprotein particles and closely related to the ubiquitously expressed SmB and B' splicing proteins. However, SmN is only expressed in a limited range of tissues and cell types such as brain, heart and early embryonic cells. The isolation of cDNA clones derived from the mRNA encoding SmN in different cell types has indicated that the brain and embryonic forms of the protein are identical and are encoded by a distinct gene to that encoding SmB and B'. It has been suggested however, that the cardiac form of SmN is encoded by a distinct mRNA which is derived from a different gene from that encoding the brain and embryonic forms of SmN. By using the polymerase chain reaction as well as cDNA cloning we have shown that this is not the case and that the cardiac, brain and embryonic forms of the protein are identical and are translated from the same mRNA encoded by a single gene. The significance of this finding is discussed in terms of the complex expression pattern of this gene and the possible functional role of SmN.
J Mol Cell Cardiol 1993 Mar
PMID:The cardiac form of the tissue-specific SmN protein is identical to the brain and embryonic forms of the protein. 851 Jan 73

The p54 protein was previously identified by its reactivity with an autoantiserum. We report here that p54 is a new member of the SR family of splicing factors, as judged from its structural, antigenic, and functional characteristics. Consistent with its identification as an SR protein, p54 can function as a constitutive splicing factor in complementing splicing-deficient HeLa cell S100 extract. However, p54 also shows properties distinct from those of other SR family members, p54 can directly interact with the 65-kDa subunit of U2 auxiliary factor (U2AF65), a protein associated with the 3' splice site. In addition, p54 interacts with other SR proteins but does not interact with the U1 small nuclear ribonucleoprotein U1-70K or the 35-kDa subunit of U2 auxiliary factor (U2AF35). This protein-protein interaction profile is different from those of prototypical SR proteins SC35 and ASF/SF2, both of which interact with U1-70K and U2AF35 but not with U2AF65. p54 promotes the use of the distal 5' splice site in E1A pre-mRNA alternative splicing, while the same site is suppressed by ASF/SF2 and SC35. These findings and the differential tissue distribution of p54 suggest that this novel SR protein may participate in regulation of alternative splicing in a tissue- and substrate-dependent manner.
Mol Cell Biol 1996 Oct
PMID:Functional properties of p54, a novel SR protein active in constitutive and alternative splicing. 881 52

The coiled body is a specific intranuclear structure of unknown function that is enriched in splicing small nuclear ribonucleoproteins (snRNPs). Because adenoviruses make use of the host cell-splicing machinery and subvert the normal subnuclear organization, we initially decided to investigate the effect of adenovirus infection on the coiled body. The results indicate that adenovirus infection induces the disassembly of coiled bodies and that this effect is probably secondary to the block of host protein synthesis induced by the virus. Furthermore, coiled bodies are shown to be very labile structures, with a half-life of approximately 2 h after treatment of HeLa cells with protein synthesis inhibitors. After blocking of protein synthesis, p80 coilin was detected in numerous microfoci that do not concentrate snRNP. These structures may represent precursor forms of the coiled body, which goes through a rapid cycle of assembly/disassembly in the nucleus and requires ongoing protein synthesis to reassemble.
Mol Biol Cell 1996 Jul
PMID:The dynamics of coiled bodies in the nucleus of adenovirus-infected cells. 886 26

We recently isolated and characterised a 69 kDa protein (69KD) found associated with spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, we report the molecular cloning of a cDNA encoding this protein, its nucleic acid binding properties and its subcellular localisation. Sequence analysis of the 69KD cDNA revealed: (1) that 69KD shares structural similarity with the human RNA binding proteins TLS and EWS (95% and 65% identity, respectively), the products of two genes frequently targeted by tumour-specific chromosomal translocations; (2) that 69KD contains a consensus RNA binding domain (CS-RBD) and three Arg/Gly-rich RNA binding motifs, structural features typical of many RNA binding proteins, in particular of hnRNP proteins; and (3) that 69KD contains a single putative Cys2/Cys2 zinc finger domain, a characteristic of many DNA-binding proteins. Consistent with its possession of these motifs, 69KD display a general nucleic acid binding activity, with a strong preference for guanyl and uridyl-rich RNA sequences, as well as for single-stranded and double-stranded DNA. The functional significance of this affinity for nucleic acids remains unclear. However, based on the established association of 69KD with the Sm core domain of snRNPs in vivo, these motifs might help mediate 69KD binding to snRNPs or be involved in some, as yet, unknown aspect of RNA metabolism. Consistent with both possibilities, 69KD is detected within typical snRNP containing subnuclear structures referred to as speckles, and is also more widely distributed throughout the nucleoplasm, as observed for many hnRNP proteins.
J Mol Biol 1996 Dec 20
PMID:Molecular cloning and subcellular localisation of the snRNP-associated protein 69KD, a structural homologue of the proto-oncoproteins TLS and EWS with RNA and DNA-binding properties. 900 Jun 15

All four spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6 and U5 contain a common structural element called the snRNP core. This core is assembled from the common snRNP proteins and the small nuclear RNA (snRNA). We have used electron microscopy to study the structure of two intermediates of the snRNP core assembly pathway: (1) the (E.F.G) protein complex, which contains only the smallest common proteins E, F and G; and (2) the subscore of U5 snRNP, in which the U5 RNA and the common proteins D1 and D2 are bound to the (E.F.G) protein complex. The general structure of the subscore was found to resemble that of the complete snRNP core, which contains the components of the subscore plus the common proteins B/B' and D3. Both the complete snRNP core and subscore particles are globular, with diameters of 7 to 8 nm. They show a characteristic accumulation of stain at the centre. However, some subscore images showed nicked outlines not seen with the complete snRNP cores. The (E.F.G) protein complex appeared as a ring, with an outer diameter of about 7 nm and a central hole 2 nm across. The molecular dimensions of the E, F and G proteins imply that the thickness of the (E.F.G) ring structure is only about 2 nm. Comparison of the (E.F.G) structure complex with the snRNP core and subcore structures implicates that a flat side of the ring-shaped (E.F.G) complex provides the assembly site(s) for the other components of the snRNP during core assembly: first for the D1 and D2 proteins (and probably the snRNA) during subscore formation, and then for the B/B' and D3 proteins in the completion of the snRNP core particle.
J Mol Biol 1997 Jan 17
PMID:Electron microscopy of assembly intermediates of the snRNP core: morphological similarities between the RNA-free (E.F.G) protein heteromer and the intact snRNP core. 902 Sep 71


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