Disease relevance of SRM1

• Conversely, neither Prp20 from ts mutant cell extracts nor wt yeast Prp20 produced in Escherichia coli, bind to dsDNA-cellulose [1].

High impact information on SRM1

• We demonstrate that prp20 and rna1 mutants are very similar, if not identical, with respect to each of these biochemical phenotypes [2].
• Previous work has demonstrated that prp20 mutants are defective in actin pre-mRNA splicing [2].
• PRP20 is related, both in structure and function, to the RCC1 gene of mammals and the PIM1 gene of Schizosaccharomyces pombe, both of which appear to regulate entry into mitosis and chromosome condensation [2].
• The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control [3].
• Dhh1 is a cytoplasmic protein and is shown to be in a complex with the mRNA degradation factor Pat1/Mtr1 and with the 5'-3' exoribonuclease Xrn1 [4].

Biological context of SRM1

• Based on the isolation of a protein kinase as a high-copy-number suppressor, the phosphorylation of Prp20p was examined [5].
• Together, these phenotypes suggest that the wild-type SRM1 product is a component of the pheromone response pathway [6].
• Thus, the SRM1 product may also have a role in the vegetative life cycle of cells [6].
• SRM1 is an essential gene and is expressed in both haploid cell types as well as in the product of their mating, a/alpha diploids [6].
• SRM1 was defined by a recessive mutation in yeast that both activates the signal transduction pathway required for mating and leads to arrest in the G1 phase of the cell cycle [7].

Associations of SRM1 with chemical compounds

• RCC1/PRP20 act as guanine nucleotide exchange factors for the nuclear Ras-like Ran/GSP1 proteins [5].
• Allele-specific suppression of a Saccharomyces cerevisiae prp20 mutation by overexpression of a nuclear serine/threonine protein kinase [5].

Physical interactions of SRM1

• Yrb2p is a nuclear protein that interacts with Prp20p, a yeast Rcc1 homologue [8].

Regulatory relationships of SRM1

• The predicted ATS1 protein contains 333 amino acids and has considerable structural homology to the products of both the mammalian mitotic control gene RCC1 and the S. cerevisiae gene SRM1/PRP20 [9].
• Yap1p export is inhibited in both rna1-1 and prp20 (RanGNRF) mutant strains, but Yap1p rapidly accumulates at the nuclear periphery after shifting rna1-1, but not other mutant cells to the non-permissive temperature [10].
• In yeast Rna1p is the GTPase activating protein for Ran (RanGAP) and Prp20p is the Ran GDP/GTP exchange factor (GEF) [11].

Other interactions of SRM1

• Only CNR1 is essential, but both code for proteins extremely similar to Ran and can suppress mtr1 mutations in allele-specific fashion [12].
• However, unlike Yrb1p, Yrb2p did not inhibit the nucleotide-releasing activity of Prp20p [13].
• In vivo labeling experiments showed that Prp20p is a phosphoprotein; however, deletion of the KSP1 kinase did not affect Prp20p phosphorylation [5].
• Overexpression of Bud5p can suppress mutations in the Gsp1p guanine nucleotide exchange factor Prp20p in Saccharomyces cerevisiae [14].
• The double mutant, srm1-1 ded1-21, could grow at 35 degrees C, but not at 37 degrees C. A revertant of srm1-1 ded1-21 that became able to grow at 37 degrees C acquired another mutation in the SRM1 gene, indicating the tight relationship between SRM1 and DED1 [15].

Analytical, diagnostic and therapeutic context of SRM1

• Site-directed mutagenesis of the yeast PRP20/SRM1 gene reveals distinct activity domains in the protein product [16].
• Immunoprecipitations and sizing-column-chromatography indicate that the Prp20 protein binds to the dsDNA column through a multicomponent complex composed of six to seven proteins, which has a collective molecular mass greater than 150,000 Da [1].
• By immunofluorescence microscopy the PRP20 protein was localized in the nucleus [17].

References