Disease relevance of TRL1

• The 95-kDa tRNA ligase has been purified to homogeneity from a strain of Escherichia coli which overexpresses the protein [1].
• Bacteriophage T4 RNA ligase (gp63) is the best-studied member of this class of enzymes, which includes yeast tRNA ligase and trypanosome RNA-editing ligases [2].

High impact information on TRL1

• The addition of purified tRNA ligase completes splicing; we therefore have reconstituted HAC1 mRNA splicing in vitro from purified components [3].
• In particular, Ire1p endonucleolytic cleavage leaves 2', 3'-cyclic phosphates, the excised exons remain associated by base pairing, and exon ligation by tRNA ligase follows the same chemical steps as for pre-tRNA splicing [4].
• We demonstrate in this study the existence of a yeast tRNA ligase-like activity in HeLa cells [5].
• These results suggest that GTP is the physiological substrate and that the Trl1 kinase has a single NTP binding site of which the P-loop is a component [6].
• Walter and co-workers (Sidrauski, C., Cox, J. S., and Walter, P. (1996) Cell, 87, 405-413) further showed that the splicing requires tRNA ligase but not spliceosome [7].

Biological context of TRL1

• The inferred amino acid sequence for tRNA ligase is not significantly homologous to that of other known proteins of similar activity [8].
• We report here the DNA sequence of the entire coding region of the Saccharomyces cerevisiae tRNA ligase gene. tRNA ligase is one of two enzymes required for tRNA splicing in yeast, and the enzyme is likely a single polypeptide with multiple activities [8].
• In addition to the tRNA ligase reading frame and several other unidentified open reading frames, we have found two open reading frames, ORF1 and ORF2, near the 5'-end of the ligase structural gene [8].
• Nucleotide sequence of ORF2: an open reading frame upstream of the tRNA ligase gene [9].
• Yeast tRNA ligase is one of two proteins required for the splicing of precursor tRNA molecules containing introns [1].

Anatomical context of TRL1

• As a key regulatory step in this signaling pathway, the mRNA encoding the UPR-specific transcription factor Hac1p becomes spliced by a unique mechanism that requires tRNA ligase but not the spliceosome [3].
• Related domains in yeast tRNA ligase, bacteriophage T4 polynucleotide kinase and RNA ligase, and mammalian myelin 2',3'-cyclic nucleotide phosphohydrolase revealed by amino acid sequence comparison [10].

Associations of TRL1 with chemical compounds

• Binding interactions between yeast tRNA ligase and a precursor transfer ribonucleic acid containing two photoreactive uridine analogues [11].
• To understand the structural requirements for the kinase-CPD domain, we performed an alanine scan of 30 amino acids that are conserved in Trl1 homologs from other fungi [12].

Enzymatic interactions of TRL1

• Trl1 also catalyzes splicing of HAC1 mRNA during the unfolded protein response [13].

Other interactions of TRL1

• Activation of Ire1p kinase induces its endoribonuclease activity to cleave unspliced HAC1 mRNA and generate exon fragments that are subsequently ligated by tRNA ligase (RLG1) [14].

References