Target intelligence / Profile preview

RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB)

Target
RTCB
Molecular classification
Enzyme, RNA ligase, RNA-processing enzyme
01

Overview

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].

Other names
RTCBC22orf28HSPC117FAAPDJ149A16.6RNA-splicing ligase RtcB homolog3'-phosphate/5'-hydroxy nucleic acid ligasefocal adhesion-associated proteinankyrin repeat domain 54tRNA-splicing ligase RtcB homolog
02

Biological functions

tRNA splicingmRNA splicing (notably XBP1 during the unfolded protein response)RNA repairProtein synthesis (indirect, via tRNA maturation)
03

Disease associations

Cancer (due to involvement in the unfolded protein response and cellular stress regulation)Neurodegeneration and other stress-associated pathologies (by analogy to its central role in RNA processing and stress granule biology)
04

Safety considerations

Essentiality for normal cellular protein synthesis may pose toxicity risks with inhibitionPotential for broad effects on RNA metabolism and stress response pathways
05

Biomarkers

XBP1 mRNA splicing status (as RTCB is necessary for XBP1 mRNA ligation during the ER stress response)

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