Disease relevance of GCD10

• The GCD10 subunit of yeast eIF-3 binds the methyltransferase-like domain of the 126 and 183 kDa replicase proteins of tobacco mosaic virus in the yeast two-hybrid system [1].
• In yeast, the formation of m(1)A58 is catalysed by the essential tRNA (m(1)A58) methyltransferase (MTase), a tetrameric enzyme that is composed of two types of subunits (Gcd14p and Gcd10p), whereas in the bacterium Thermus thermophilus the enzyme is a homotetramer of the TrmI polypeptide [2].

High impact information on GCD10

• Whereas deletion of TRF4 leads to stabilization of tRNA(i)(Met), overexpression of Trf4p destabilizes the hypomodified tRNA(i)(Met) in trm6 cells [3].
• Remarkably, the lethality of a GCD10 deletion was suppressed by high-copy-number IMT4, indicating that its role in expression of mature tRNAiMet is the essential function of Gcd10p [4].
• The phenotypes of gcd10 mutants were suppressed by high-copy-number IMT genes, encoding initiator methionyl tRNA (tRNAiMet), or LHP1, encoding the yeast homolog of the human La autoantigen [4].
• Interestingly, gcd10 and gcd14 mutations had no effect on processing or accumulation of elongator tRNAMet, which also contains m1A at position 58, suggesting a unique requirement for this base modification in initiator maturation [4].
• GCD10, a translational repressor of GCN4, is the RNA-binding subunit of eukaryotic translation initiation factor-3 [5].

Biological context of GCD10

• Dosage suppressors of gcd10 mutations, encoding tRNAiMet (hcIMT1 to hcIMT4; hc indicates that the gene is carried on a high-copy-number plasmid) or a homologue of human La protein implicated in tRNA 3'-end formation (hcLHP1), also suppressed gcd14 mutations [6].
• In this study we have identified the human homologs of the yeast m(1)A Mtase through amino acid sequence identity and complementation of trm6 and trm61 mutant phenotypes [7].
• These findings are consistent with a role for a GCD10-like protein in the TMV replicase complex and suggest that, in TMV-infected cells, the machinery of virus replication and protein synthesis may be closely connected [1].

Associations of GCD10 with chemical compounds

• Supporting this prediction, affinity-purified Gcd10p/Gcd14p complexes used AdoMet as a methyl donor to synthesize m(1)A in either total tRNA or purified tRNA(i)(Met) lacking only this modification [8].
• The absence of m(1)A from all tRNAs in Saccharomyces cerevisiae mutants lacking Gcd10p elicits severe defects in processing and stability of initiator methionine tRNA (tRNA(i)(Met)) [8].
• 1-Methyladenosine modification at position 58 of tRNA is catalyzed by a two-subunit methyltransferase composed of Trm6p and Trm61p in Saccharomyces cerevisiae [9].

Physical interactions of GCD10

• Using this approach, we identified a previously undetected m1A modification in GlnCTG tRNA, the formation of which is catalyzed by the Gcd10/Gcd14 complex. complex [10].

Analytical, diagnostic and therapeutic context of GCD10

• The identification of the yeast GCD10 gene as the structural gene for the zeta subunit of yeast eIF-3(1) and the analysis of mutant phenotypes has opened the door to the genetic dissection of the eIF-3 protein complex [11].
• Western blotting showed that the two largest of these proteins are the TMV-L-encoded 183- and 126-kDa replication proteins and that the 56-kDa protein is related to the 54.6-kDa GCD10 protein, the RNA-binding subunit of yeast eIF-3 [12].

References