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RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB) is an essential enzyme that joins RNA molecules with a 3'-phosphate and 5'-hydroxyl terminus, in a GTP-dependent reaction distinct from canonical ATP-dependent RNA ligases[1][2]. In humans, RTCB serves as the catalytic subunit of the tRNA ligase complex and is required for tRNA splicing, the repair of certain RNA damage, and the unconventional splicing of XBP1 mRNA during the endoplasmic reticulum unfolded protein response[2][3]. Activation of RTCB involves the formation of a covalent guanylylated intermediate, a reaction enabled by Archease and divalent metal ions, and the enzyme is unique in its structure and mechanism compared to other nucleic acid ligases[1][2]. Owing to its roles in RNA metabolism, protein synthesis, and cellular stress adaptation, RTCB is required for cell viability and is implicated in human disease, including cancer and potentially other conditions where RNA processing is disrupted[3][4].
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