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RNA Ligases: Function, Mechanism, and Sequence Conservation

Eric A. Arn, John Abelson


Enzymes that catalyze the ligation of RNA molecules via phosphodiester bonds have been detected in organisms of all major phyla. Beginning with the observation of RNA-joining activity in extracts of bacteriophage-infected Escherichia coli (Silber et al. 1972), six different types of RNA ligase have been discovered, falling into four distinct mechanistic classes. Specific metabolic functions have been assigned to four of these enzymes: (1) T4 RNA ligase, which repairs nicks in the tRNAs of phage-infected E. coli, (2) eukaryotic tRNA ligase, which joins tRNA half-molecules produced by the excision of introns from tRNA precursors, (3) archaeal stable RNA ligase, which is involved in the splicing of introns from both tRNA and rRNA, and (4) an RNA ligase responsible for joining mRNA fragments during RNA editing in kinetoplastids. The in vivo functions and substrates of the metazoan-specific animal pathway RNA ligase and the E. coli 2′–5′ RNA ligase remain to be determined.

The first mechanistic class of RNA ligase is exemplified by T4 RNA ligase, which requires the multiple enzymatic activities of T4 polynucleotide kinase (PNK) in trans to complete physiologically relevant RNA joining. Together these enzymes execute a complex reaction pathway utilizing two equivalents of nucleotide triphosphates (NTPs) for each bond formed, and incorporating a phosphate derived from an NTP cofactor into the ligation junction. Available evidence implies that the kinetoplastid editing RNA ligase is mechanistically identical to T4 RNA ligase. A nearly identical pathway is used by the second class of RNA ligase, the tRNA ligases. These enzymes,...

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