RTCB

RTCB
Identifiers
Aliases	RTCB, C22orf28, DJ149A16.6, FAAP, HSPC117, RNA 2',3'-cyclic phosphate and 5'-OH ligase
External IDs	OMIM: 613901; MGI: 106379; HomoloGene: 36344; GeneCards: RTCB; OMA:RTCB - orthologs
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q12.3 Start 32,387,582 bp[1] End 32,412,248 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 41.81 cM Start 85,774,501 bp[2] End 85,793,687 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa islet of Langerhans mucosa of ileum duodenum rectum skin of leg skin of abdomen beta cell skin of arm smooth muscle tissue Top expressed in primitive streak mandibular prominence maxillary prominence endocardial cushion facial motor nucleus vestibular sensory epithelium efferent ductule lobe of prostate Rostral migratory stream vas deferens More reference expression data BioGPS n/a
Gene ontology Molecular function vinculin binding nucleotide binding RNA ligase (ATP) activity ligase activity protein binding ATP binding RNA ligase activity metal ion binding RNA binding Cellular component cytoplasm tRNA-splicing ligase complex nuclear envelope endoplasmic reticulum membrane nucleus nucleoplasm cytosol intracellular membrane-bounded organelle Biological process RNA processing tRNA splicing, via endonucleolytic cleavage and ligation tRNA processing tRNA exon ligation utilizing 2',3' cyclic phosphate of 5'-exon as source of linkage phosphate in utero embryonic development placenta development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51493 28088 Ensembl ENSG00000100220 ENSMUSG00000001783 UniProt Q9Y3I0 Q99LF4 RefSeq (mRNA) NM_014306 NM_145422 RefSeq (protein) NP_055121 NP_663397 Location (UCSC) Chr 22: 32.39 – 32.41 Mb Chr 10: 85.77 – 85.79 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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

As of June 2019^[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

Protein family

tRNA splicing ligase RtcB
Identifiers
Symbol	RtcB
Pfam	PF01139
InterPro	IPR001233
PROSITE	PS01288
CATH	1uc2
SCOP2	1uc2 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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

1. GRCh38: Ensembl release 89: ENSG00000100220 – Ensembl, May 2017
2. 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

• Pérez-González A, Pazo A, Navajas R, Ciordia S, Rodriguez-Frandsen A, Nieto A (2014). "hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel transcription-dependent shuttling RNA-transporting complex". PLOS ONE. 9 (3) e90957. Bibcode:2014PLoSO...990957P. doi:10.1371/journal.pone.0090957. PMC 3946611. PMID 24608264.
• Ma H, Qi MY, Zhang X, Zhang YL, Wang L, Li ZQ, et al. (June 2014). "HSPC117 is regulated by epigenetic modification and is involved in the migration of JEG-3 cells". International Journal of Molecular Sciences. 15 (6): 10936–49. doi:10.3390/ijms150610936. PMC 4100190. PMID 24941254.
• Jurkin J, Henkel T, Nielsen AF, Minnich M, Popow J, Kaufmann T, et al. (December 2014). "The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells". The EMBO Journal. 33 (24): 2922–36. doi:10.15252/embj.201490332. PMC 4282640. PMID 25378478.

External links

• MetaCyc: CPLX-9136: Homo sapiens tRNA-splicing ligase complex (GO:0072669)