Disease relevance of HMT1

• Characterization of a novel barley protein, HCP1, that interacts with the Brome mosaic virus coat protein [1].

High impact information on HMT1

• Furthermore, RNA in situ hybridization analysis demonstrates that loss of Hmt1 results in slowed release of HSP104 mRNA from the sites of transcription [2].
• Moreover, loss of Hmt1 affects interactions between mRNA-binding proteins and Tho2, a component of the TREX (transcription/export) complex that is important for transcriptional elongation and recruitment of mRNA export factors [2].
• Hmt1 is the major type I arginine methyltransferase in the yeast Saccharomyces cerevisiae and facilitates the nucleocytoplasmic transport of mRNA-binding proteins through their methylation [2].
• Hmt1p methylates both Npl3p and Hrp1p, which are shuttling hnRNPs involved in mRNA processing and export [3].
• Furthermore, we find a genetic relationship between Hmt1p and cap-binding protein 80 (CBP80) [3].

Biological context of HMT1

• HMT1 is not required for normal cell viability except when NPL3 is also defective [4].
• Amino acid changes in the putative Hmt1p S-adenosyl-L-methionine-binding site were generated and shown to be unable to catalyze methylation of Npl3p in vitro and in vivo or to restore growth to strains that require HMT1 [5].
• The yeast Saccharomyces cerevisiae contains one major arginine methyltransferase, Hmt1p/Rmt1p, which is not essential for normal cell growth [5].
• When compared with Rmt1, another putative yeast HMT, Dot1 shows very distinct substrate specificity [6].
• A point mutation was identified (E117G) in Rmt1 that renders the enzyme susceptible to selective inhibition by the SAH analogues [7].

Anatomical context of HMT1

• Immunoblot analysis of subcellular fractions indicates that the native HMT1 polypeptide is associated with the vacuolar membrane [8].
• The pump of S. pombe is distinct from the previously identified vacuolar pump, hmt1p, for transporting cadystin peptides into vacuoles of S. pombe [9].

Associations of HMT1 with chemical compounds

• We first developed an in vivo assay to identify proteins methylated by the Hmt1 arginine methyltransferase [10].
• Following SDS polyacrylamide electrophoresis, 11 distinct proteins were identified as substrates for the Hmt1 methyltransferase [10].
• Vacuolar uptake of Cd2+ and of a glutathione conjugate were also observed, but are not attributable to HMT1 [8].
• Intact yeast cells lacking RMT1, the gene encoding the protein omega-NG-arginine methyltransferase, were labeled with the methyl donor S-adenosyl-L-[methyl-3H]methionine [11].
• Npl3 with all 15 RGG arginines mutated to lysine exited the nucleus independent of Hmt1, indicating a direct effect of methylation on Npl3 transport [12].

Physical interactions of HMT1

• However, cells missing HMT1 and also bearing mutations in the mRNA-binding proteins Npl3p or Cbp80p can no longer survive, providing genetic backgrounds in which to study Hmt1p function [5].
• Air2p also has a RING finger domain and was bound to Hmt1p [13].

Regulatory relationships of HMT1

• Overexpression of Air1p repressed the Hmt1p-dependent growth of cells [13].
• Nab2p is required for poly(A) RNA export in Saccharomyces cerevisiae and is regulated by arginine methylation via Hmt1p [14].

Other interactions of HMT1

• We demonstrate that Npl3p is methylated by Hmt1p both in vivo and in vitro [4].
• The observation that three nucleolar proteins are modified by Hmt1p but are not exported from the nucleolus implies an alternate role for arginine methylation [10].
• Genome-wide location analysis shows that Hmt1 is bound to specific functional gene classes, many of which are also bound by Tho2 and other mRNA-processing factors [2].
• Furthermore, we show that Nab2p is modified within its RGG domain by the type I protein-arginine methyltransferase, Hmt1p [14].
• We found that we could distinguish PRMT family members by their sensitivity to these reagents; JBP1/PRMT5 and Hsl7 methyltransferases were inhibited in a similar manner as PRMT3, whereas Rmt1, PRMT1, and CARM1/PRMT4 were not affected [15].

Analytical, diagnostic and therapeutic context of HMT1

• Northern blot analysis revealed that multicopies of the yeast and human HCP1, as well as TGFR, resulted in an increase in the IN01 mRNA level in the yeast mutant [16].
• HCP1 was found predominantly in the soluble fractions after differential centrifugation of BMV-infected and mock-inoculated barley tissues [1].

References