Disease relevance of TRM1

• Cloning of the P.furiosus TRM1 gene in an Escherichia coli expression vector allowed expression of the recombinant protein (pfTrm1p) with an apparent molecular mass of 42 kDa [1].
• The deduced amino acid sequence of this newly identified gene shares significant similarity with the TRM1- like genes of three other archaea (Methanococcus jannaschii, Methanobacterium thermoautotrophicum and Archaeoglobus fulgidus), one eukaryon (Caenorhabditis elegans) and one hyperthermophilic eubacterium (Aquifex aeolicus) [1].

High impact information on TRM1

• The TRM1 gene of Saccharomyces cerevisiae encodes a tRNA modification enzyme, N2,N2-dimethylguanosine-specific tRNA methyltransferase, which modifies both mitochondrial and cytoplasmic tRNAs [2].
• The DNA sequence of the TRM1 locus and the 5' ends of mRNAs expressed from this gene have been determined [3].
• In addition, TRM11 interacts genetically with TRM1, thus suggesting that the absence of m(2)G10 and m(2)(2)G26 affects tRNA metabolism or functioning [4].
• The TRM1 gene of Saccharomyces cerevisiae codes for a tRNA modification enzyme, N2,N2-dimethylguanosine-specific tRNA methyltransferase (m2(2)Gtase), shared by mitochondria and nuclei [5].
• Isolation and characterization of the TRM1 locus, a gene essential for the N2,N2-dimethylguanosine modification of both mitochondrial and cytoplasmic tRNA in Saccharomyces cerevisiae [6].

Biological context of TRM1

• An open reading frame in this TRM1 gene is essential for complementation of the trm1 phenotype [6].
• The required identity elements in yeast tRNA for dimethylation under in vitro conditions by the yeast tRNA(m2(2)G26)-methyltransferase (the TRM1 gene product) are comprised of two G-C base pairs at positions G10-C25 and C11-G24 in the D-stem together with a variable loop of at least five nucleotides [7].
• Comparatively short N- or C-terminal deletions from the 570 amino acid long Trm1 polypeptide decreased or eliminated the enzyme activity, as did some point mutations within these regions [8].

Associations of TRM1 with chemical compounds

• Point and deletion mutations eliminate one or both methyl group transfers catalysed by the yeast TRM1 encoded tRNA (m22G26)dimethyltransferase [8].

Other interactions of TRM1

• Other tRNA modification enzymes interacting with tRNA(Ser)CGA in the maturation process, such as Pus4p, Trm1 p, and Trm3p were essential or important for growth of the tRNA(Ser)CGA mutants [9].

References