Disease relevance of MOD5

• That MOD5 sequences are expressed in Escherichia coli and can complement an N6-(delta 2-isopentenyl)-2-methylthioadenosine-deficient E. coli mutant leads us to conclude that MOD5 is the structural gene for delta 2-isopentenyl pyrophosphate:tRNA isopentenyl transferase [1].
• Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer [2].
• The tRNA isopentenyltransferase from maize root tips and kernels catalyzes the incorporation of 2-isopentenyl groups into (Ap)3-7A, endogenous bulk oligonucleotos from maize root tips and kernels, and into poly(A), RNA from MS-2 phages and, to a very low extent, into adenosine [3].

High impact information on MOD5

• Thus, Erg20p appears to affect nonsense suppression by competing with Mod5p for substrate [4].
• The Saccharomyces cerevisiae Mod5 protein catalyzes isopentenylation of A to i(6)A on tRNAs in the nucleus, cytosol, and mitochondria [4].
• Changing the distribution of Mod5p so that less Mod5p is present in the cytosol decreases i(6)A on cytosolic tRNAs and alters tRNA-mediated nonsense suppression [4].
• The substrate for Mod5p, dimethylallyl pyrophosphate, is also a substrate for Erg20p that catalyzes an essential step in sterol biosynthesis [4].
• Extending the 5' ends of the MOD5 mRNA to include leader sequences of the ADH1 (alcohol dehydrogenase defective) transcript produces significant changes in the choice of AUGs [5].

Biological context of MOD5

• DNA sequence analysis of MOD5 reveals an open reading frame of 428 amino acids [6].
• DNA sequence and transcript mapping of MOD5: features of the 5' region which suggest two translational starts [6].
• By this assay, Mod5p may contain more than one region that functions as cytoplasmic retention and/or nuclear export sequences [7].
• The mdp1 mutants were previously found to change the mitochondrial/cytosolic distribution of Mod5p-I, the tRNA modifying enzyme, and to affect fluid phase endocytosis [8].
• Expression in S. cerevisiae showed that the gene can complement the anti-suppressor phenotype of a mutant that lacks MOD5, the intrinsic tRNA isopentenyltransferase gene [9].

Anatomical context of MOD5

• Two inframe ATGs of the MOD5 gene are used for initiation of translation, and the form of the protein translated from the first AUG is imported into mitochondria [5].
• Mutations altering the mitochondrial-cytoplasmic distribution of Mod5p implicate the actin cytoskeleton and mRNA 3' ends and/or protein synthesis in mitochondrial delivery [10].

Associations of MOD5 with chemical compounds

• MOD5 translation initiation sites determine N6-isopentenyladenosine modification of mitochondrial and cytoplasmic tRNA [11].
• The product of the MOD5 gene is isopentenyl pyrophosphate: tRNA isopentenyl transferase and the product of the CCA1 gene is ATP (CTP): tRNA nucleotidyltransferase [12].
• The ts phenotype, hygromycin B and paromomycin sensitivity are suppressed by pmal-t, but the pH sensitivity, the effect of mdp1 on Mod5p-I cytoplasmic/mitochondrial localization and endocytosis are not [8].

Other interactions of MOD5

• maf1 mutation alters the subcellular localization of the Mod5 protein in yeast [13].
• In these studies, we fused MOD5 sequences encoding N-terminal regions to genes encoding passenger proteins, pseudomature COXIV and dihydrofolate reductase, and studied the ability of these chimeric proteins to be imported into mitochondria both in vivo and in vitro [14].

Analytical, diagnostic and therapeutic context of MOD5

• We used indirect immunofluorescence and cell fractionation to locate the MOD5 isozymes in yeast [14].
• Sequence analysis of this locus revealed an open reading frame with strong homology to the miaA locus of Escherichia coli and the mod5 locus of Saccharomyces cerevisiae [15].
• Immunofluorescence data suggest that the mutation causes mislocalization of the Mod5p-I to the nucleus [13].

References