Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SRP1-1 mutation is an allele-specific dominant suppressor of temperature-sensitive mutations in the zinc-binding domain of the A190 subunit of Saccharomyces cerevisiae RNA polymerase I (Pol I). We found that it also suppresses temperature-sensitive mutations in the zinc-binding domain of the Pol I A135 subunit. This domain had been suggested to be in physical proximity to the A190 zinc-binding domain. We have cloned the SRP1 gene and determined its nucleotide sequence. The gene encodes a protein of 542 amino acids consisting of three domains: the central domain, which is composed of eight (degenerate) 42-amino-acid contiguous tandem repeats, and the surrounding N-terminal and C-terminal domains, both of which contain clusters of acidic and basic amino acids and are very hydrophilic. The mutational alteration (P219Q) responsible for the suppression was found to be in the central domain. Using antibody against the SRP1 protein, we have found that SRP1 is mainly localized at the periphery of the nucleus, apparently more concentrated in certain regions, as suggested by a punctate pattern in immunofluorescence microscopy. We suggest that SRP1 is a component of a larger macromolecular complex associated with the nuclear envelope and interacts with Pol I either directly or indirectly through other components in the structure containing SRP1.
 ...
PMID:Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. 144 93

We used the yeast interactive trap system to identify a cellular protein which interacts with the nucleoprotein of influenza A viruses. This protein, nucleoprotein interactor 1 (NPI-1) is the human homolog of the yeast protein SRP1. SRP1 was previously identified as a suppressor of temperature-sensitive RNA polymerase I mutations (R. Yano, M. Oakes, M. Yamaghishi, J. Dodd, and M. Nomura, Mol. Cell. Biol. 12, 5640-5651, 1992). A full-length cDNA clone of NPI-1 was generated from HeLa cell poly A + RNA. The viral nucleoprotein, which had been partially purified from influenza A/PR/8/34 virus-infected embryonated eggs, could be coprecipitated from solution by glutathione agarose beads complexed with a bacterially expressed glutathione-S-transferase-NPI-1 fusion protein, confirming the results of the yeast genetic system. Antisera raised against NPI-1 identified a 60-kDa polypeptide from total cellular extracts of both HeLa and MDBK cells. The viral nucleoprotein was coimmunoprecipitated from influenza A/WSN/33 virus-infected MDBK cells by anti-NPI-1 sera, demonstrating an interaction of these two proteins in infected cells. Similarly, NPI-1 was coimmunoprecipitated from MDBK cells by anti-NP sera. These experiments suggest that NPI-1 plays a role during influenza virus replication.
 ...
PMID:NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein. 783 67

SRP1, a suppressor of certain temperature-sensitive mutations in RNA polymerase I in Saccharomyces cerevisiae, encodes a protein that is associated with nuclear pores. By using a system of conditional SRP1 expression and by isolating temperature-sensitive srp1 mutants, we have demonstrated that Srp1p is essential for maintenance of the crescent-shaped nucleolar structure, RNA transcription, and the proper functions of microtubules as inferred from analysis of nuclear division/segregation and immunofluorescence microscopy of microtubules. Different mutant alleles showed significantly different phenotypes in relation to these apparently multiple functional roles of the protein. We have also found that eight imperfect 42-amino-acid tandem repeats present in Srp1p are similar to the 42-amino-acid repeats in armadillo/plakoglobin/beta-catenin proteins present in adhesive junction complexes of higher eukaryotes. We discuss this similarity in connection with the observed pleiotropic effects of srp1 mutations.
 ...
PMID:Yeast Srp1p has homology to armadillo/plakoglobin/beta-catenin and participates in apparently multiple nuclear functions including the maintenance of the nucleolar structure. 804 13

Genes for immunoglobulins and T-cell receptor are generated by a process known as V(D)J recombination. This process is highly regulated and mediated by the recombination activating proteins RAG-1 and RAG-2. By the use of the two-hybrid protein interaction system, we isolated a human protein that specifically interacts with RAG-1. This protein is the human homologue of the yeast SRP1 (suppressor of a temperature-sensitive RNA polymerase I mutation). The SRP1-1 mutation is an allele-specific dominant suppressor of a temperature-sensitive mutation in the zinc binding domain of the 190-kDa subunit of Saccharomyces cerevisiae RNA polymerase I. The human SRP cDNA clone was used to screen a mouse cDNA library. We obtained a 3.9-kbp cDNA clone encoding the mouse SRP1. The open reading frame of this cDNA encodes a 538-amino acid protein with eight degenerate repeats of 40-45 amino acids each. The mouse and human SRP1 are 98% identical, while the mouse and yeast SRP1 have 48% identity. After cotransfection of the genes encoding RAG-1 and human SRP1 into 293T cells, a stable complex was evident. Deletion analysis indicated that the region of the SRP1 protein interacting with RAG-1 involved four repeats. The domain of RAG-1 that associates with SRP1 mapped N-terminal to the zinc finger domain. Because this region of RAG-1 is not required for recombination and SRP1 appears to be bound to the nuclear envelope, we suggest that this interaction helps to localize RAG-1.
 ...
PMID:RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1. 805 33

Protein p120 is a proliferation-related nucleolar protein, which is detectable early in the G1-phase of the cell cycle and peaks early in the S-phase. Most human malignant tumor cells contain much higher levels of protein p120 than do normal resting cells. To learn more about p120-associated proteins, a yeast two-hybrid screen was carried out using protein p120 as the bait. Five positive clones were identified from 2 million clones for further analysis. Three of them encoded portions of the same protein, which had identity to human SRP1. The recombinant p120 and HSRP1 proteins produced in Sf9 cells are associated with each other, confirming the results of the yeast genetic assay. Protein SRP1 was originally characterized as a suppressor of RNA polymerase I mutations, and recently human SRP1 was identified as a receptor for nuclear localization sequences. In the present study, use of deletion mutations revealed that the binding of human SRP1 to p120 required the p120 nuclear localization signal (amino acids 96-119) and the C-terminus of human SRP1 (amino acids 453-491).
 ...
PMID:Human proliferation-related protein p120 interacts with HSRP1. 921 83

The accumulation of karyophilic proteins in the nucleus requires cytoplasmic factors. Cell-free systems that reconstitute nuclear protein import have been used to identify several of these factors and to define the biochemical requirements for the import process. Recently, one factor has been purified and cloned from Xenopus and identified as a homologue of the 'suppressor of RNA polymerase l' (SRP1) gene originally described in yeast. This factor belongs to a closely related group of proteins that may share similar functions in nuclear protein transport.
 ...
PMID:The importance of importin. 1473 46