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RTCB

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RTCB
Identifiers
AliasesRTCB, C22orf28, DJ149A16.6, FAAP, HSPC117, RNA 2',3'-cyclic phosphate and 5'-OH ligase
External IDsOMIM: 613901; MGI: 106379; HomoloGene: 36344; GeneCards: RTCB; OMA:RTCB - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_014306

NM_145422

RefSeq (protein)

NP_055121

NP_663397

Location (UCSC)Chr 22: 32.39 – 32.41 MbChr 10: 85.77 – 85.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

RNA 2',3'-cyclic phosphate and 5'-OH ligase is a protein that in humans is encoded by the RTCB gene.[5] It is found in the stress granule of cells.[6]

Structure

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As of June 2019, 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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Protein family

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tRNA splicing ligase RtcB
Identifiers
SymbolRtcB
PfamPF01139
InterProIPR001233
PROSITEPS01288
CATH1uc2
SCOP21uc2 / SCOPe / SUPFAM
Available protein structures:
PDB  IPR001233 PF01139 (ECOD; PDBsum)  
AlphaFold

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]

References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000100220 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001783 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: RNA 2',3'-cyclic phosphate and 5'-OH ligase". Retrieved 6 June 2019.
  6. Jain S, Wheeler JR, Walters RW, Agrawal A, Barsic A, Parker R (January 2016). "ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure". Cell. 164 (3): 487–98. Bibcode:2016Cell..164..487J. doi:10.1016/j.cell.2015.12.038. PMC 4733397. PMID 26777405.
  7. Desai KK, Bingman CA, Phillips GN, Raines RT (April 2013). "Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation". Biochemistry. 52 (15): 2518–25. doi:10.1021/bi4002375. PMC 3670941. PMID 23560983.
  8. Gerber JL, Morales Guzmán SI, Worf L, Hubbe P, Kopp J, Peschek J (16 March 2024). "Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease". Nature Communications. 15 (1) 2378. Bibcode:2024NatCo..15.2378G. doi:10.1038/s41467-024-46568-2. eISSN 2041-1723. PMC 10944509. PMID 38493148.
  9. Tanaka N, Shuman S (March 2011). "RtcB is the RNA ligase component of an Escherichia coli RNA repair operon". The Journal of Biological Chemistry. 286 (10): 7727–31. doi:10.1074/jbc.C111.219022. PMC 3048659. PMID 21224389.
  10. Tanaka N, Meineke B, Shuman S (September 2011). "RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo". The Journal of Biological Chemistry. 286 (35): 30253–7. doi:10.1074/jbc.C111.274597. PMC 3162383. PMID 21757685.
  11. Popow J, Englert M, Weitzer S, Schleiffer A, Mierzwa B, Mechtler K, et al. (February 2011). "HSPC117 is the essential subunit of a human tRNA splicing ligase complex". Science. 331 (6018): 760–4. Bibcode:2011Sci...331..760P. doi:10.1126/science.1197847. hdl:11858/00-001M-0000-0011-5682-B. PMID 21311021. S2CID 1881494.
  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.

Further reading

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