As of June2019[update], no crystal structure of the human RTCB is known, but homology models built from other RtcB-family ligases are available (Swiss-model: Q9Y3I0). The structure of Pyrococcus horikoshii RtcB, which uses GTP instead of ATP, shows two manganese (Mn2+) cofactors, and a mechanism involving a covalently linked GTP-histidine-RtcB intermediate. The residue involved, H404, is conserved in human RTCB as H428.[7]
Crystal structures of human RTCB in complex with human archease demonstrates that archease is essential for the activation of RTCB.[8]
Function
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RTCB belongs to the RtcB family of ATP-dependent RNA ligases, named after the eponymous protein in E. coli. The bacterial RtcB acts as a tRNA ligase, rejoining broken stem-loops in case of damage.[9] It is also able to catalyse RNA splicing.[10]
The eukaryotic homologs of RtcB, including the human RTCB protein, participates in the tRNA-splicing ligase complex.[11]
Recently, RTCB was suggested to be involved in splicing DNA transposons in C. elegans and human cells. [12]
↑Zhao LW, Nardone C, Chang C, Paulo JA, Elledge SJ, Kennedy S (2026). "An RNA splicing system that excises DNA transposons from animal mRNAs". Nature. 649 (8096): 496–504. doi:10.1038/s41586-025-09853-8.
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