Reaction: ATP + (ribonucleotide)n-3'-hydroxyl + 5'-phospho-(ribonucleotide)m = (ribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [RNA ligase]-L-lysine = [RNA ligase]-N6-(5'-adenylyl)-L-lysine + diphosphate
(1b) [RNA ligase]-N6-(5'-adenylyl)-L-lysine + 5'-phospho-(ribonucleotide)m = 5'-(5'-diphosphoadenosine)-(ribonucleotide)m + [RNA ligase]-L-lysine
(1c) (ribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(ribonucleotide)m = (ribonucleotide)n+m + AMP
Other name(s): polyribonucleotide synthase (ATP); RNA ligase; polyribonucleotide ligase; ribonucleic ligase; poly(ribonucleotide):poly(ribonucleotide) ligase (AMP-forming)
Systematic name: poly(ribonucleotide)-3'-hydroxyl:5'-phospho-poly(ribonucleotide) ligase (ATP)
Comments: The enzyme catalyses the ligation of RNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in RNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[RNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37353-39-2
References:
1. Silber, R., Malathi, V.G. and Hurwitz, J. Purification and properties of bacteriophage T4-induced RNA ligase. Proc. Natl. Acad. Sci. USA 69 (1972) 3009-3013. [PMID: 4342972]
2. Cranston, J.W., Silber, R., Malathi, V.G. and Hurwitz, J. Studies on ribonucleic acid ligase. Characterization of an adenosine triphosphate-inorganic pyrophosphate exchange reaction and demonstration of an enzyme-adenylate complex with T4 bacteriophage-induced enzyme. J. Biol. Chem. 249 (1974) 7447-7456. [PMID: 4373468]
3. Sugino, A., Snoper, T.J. and Cozzarelli, N.R. Bacteriophage T4 RNA ligase. Reaction intermediates and interaction of substrates. J. Biol. Chem. 252 (1977) 1732-1738. [PMID: 320212]
4. Romaniuk, P.J. and Uhlenbeck, O.C. Joining of RNA molecules with RNA ligase. Methods Enzymol. 100 (1983) 52-59. [PMID: 6194411]
5. Ho, C.K., Wang, L.K., Lima, C.D. and Shuman, S. Structure and mechanism of RNA ligase. Structure 12 (2004) 327-339. [PMID: 14962393]
6. Nandakumar, J., Shuman, S. and Lima, C.D. RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward. Cell 127 (2006) 71-84. [PMID: 17018278]