Affinage

Showing RTCB — HSPC117 is a alias.

RTCB

RNA-splicing ligase RTCB · UniProt Q9Y3I0

Length
505 aa
Mass
55.2 kDa
Annotated
2026-06-10
52 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RTCB (HSPC117) is the essential catalytic subunit of the human tRNA ligase complex, a noncanonical 3'-5' RNA ligase that seals broken RNA ends bearing 2',3'-cyclic phosphate (or 3'-phosphate) and 5'-OH termini during RNA splicing and repair (PMID:21311021, PMID:21224389). It operates through a unique three-step, GTP- and Mn²⁺-dependent mechanism: an active-site histidine (His337 in human, His404 in archaeal orthologs) reacts with GTP to form a covalent RtcB-(histidinyl-N)-GMP intermediate, guanylate is transferred to the RNA 3'-phosphate yielding an RNA-(3')pp(5')G species, and the 5'-OH then attacks the 3'-ppG end to form the splice junction (PMID:22474365, PMID:22730297). Crystal and cryo-EM structures resolved snapshots of this guanylylation pathway, defined a two-metal active site whose cofactor permissiveness depends on M2 coordination geometry, and mapped the substrate contacts that engage the RNA backbone and 5'-OH nucleophile (PMID:22949672, PMID:23560983, PMID:33619169, PMID:36130078). This ligase activity is required for maturation of intron-containing pre-tRNA and for splicing of XBP1 mRNA during the IRE1α branch of the ER unfolded protein response, where ligase-dead RTCB fails to rescue splicing (PMID:21311021, PMID:25087875, PMID:25366321). RTCB additionally repairs stress-induced tRNA fragments (tiRNAs) back to full-length tRNAs, thereby restraining tiRNA accumulation under oxidative stress (PMID:36361884). Within the ligase complex RTCB partners with DDX1, FAM98B, and CGI-99 in a helical bundle, and the vertebrate-specific subunit Ashwin provides the nuclear localization signal that directs FAM98B-containing complexes to the nucleus for pre-tRNA splicing, while FAM98A/FAM98C-containing complexes remain cytoplasmic for XBP1 mRNA splicing [PMID:bio_10.1101_2025.08.01.668197, PMID:bio_10.1101_2025.08.01.668163]. The cofactor Archease activates RTCB by reaching into its active site to coordinate GTP and metal, promoting formation of the RTCB-GMP intermediate and converting the enzyme from single- to multiple-turnover (PMID:24435797, PMID:26385509, PMID:38493148). RTCB activity is further tuned by tyrosine phosphorylation at Y306 by c-Abl (reversed by PTP1B), which perturbs the RTCB-IRE1α interaction and shifts UPR signaling between adaptive and pro-death outcomes (PMID:35193953), and by USP45-mediated deubiquitination that stabilizes the protein (PMID:41468936). Beyond canonical splicing, RTCB ligase activity functions in a spliceosome-independent pathway that excises DNA transposons from host mRNAs via the bridging factors CAAP1 and AKAP17A [PMID:bio_10.1101_2025.02.14.638102].

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 High

    Establishing what enzyme directly ligates tRNA exons answered a long-standing gap in human RNA biology, identifying RTCB as the catalytic ligase of tRNA splicing.

    Evidence Activity-guided purification from HeLa extracts plus RNAi in vitro and in vivo; parallel in vitro reconstitution with E. coli RtcB on tRNA-like substrates and yeast trl1Δ complementation

    PMID:21224389 PMID:21311021 PMID:21757685

    Open questions at the time
    • Catalytic mechanism not yet resolved at this stage
    • Substrate range beyond tRNA only inferred from yeast complementation
  2. 2012 High

    Defining the catalytic chemistry distinguished RTCB from all classical ligases, revealing a GTP/Mn²⁺-dependent three-step pathway through a covalent His-GMP intermediate.

    Evidence In vitro stepwise biochemical assays, mass-spec identification of covalent intermediates, His337 mutagenesis, kinetics with GTP analogs, and crystal structures of P. horikoshii RtcB with Mn²⁺ and bound GMP

    PMID:22045815 PMID:22474365 PMID:22730297 PMID:22949672

    Open questions at the time
    • Substrate RNA contacts not yet visualized
    • How cofactors are loaded/activated unresolved
  3. 2013 High

    Capturing structural snapshots of the guanylylation pathway resolved how RTCB uses a two-metal mechanism that converged independently with ATP/Mg ligases.

    Evidence X-ray crystallography of pre-GTP, GTPαS-bound, and covalent His404-GMP states

    PMID:23560983

    Open questions at the time
    • Performed on archaeal ortholog, not human enzyme
    • RNA substrate engagement not captured
  4. 2014 High

    Knockout/rescue experiments established RTCB as the physiological UPR ligase, directly linking its catalytic activity to XBP1/xbp-1 mRNA splicing and stress adaptation.

    Evidence RTCB knockout cells with ligase-dead rescue and in vitro splicing in mammals; C. elegans rtcb mutants with xbp-1 splicing and lifespan readouts plus neuroprotection epistasis

    PMID:25087875 PMID:25366321 PMID:25429148

    Open questions at the time
    • How RTCB is recruited to the IRE1α-cleaved XBP1 substrate not defined here
    • Functions independent of tRNA/UPR noted but not mechanistically explained
  5. 2014 High

    Identifying Archease as an activating cofactor explained how RTCB achieves multiple-turnover catalysis and broadened its NTP specificity.

    Evidence In vitro ligation assays with purified RtcB and Archease, mutagenesis of both proteins, NTP specificity tests, and Archease crystal structure; cross-species turnover measurements

    PMID:24435797 PMID:26385509

    Open questions at the time
    • Structural basis of Archease entry into the active site not yet resolved
    • Regulation of Archease availability in cells unknown
  6. 2014 Medium

    Co-IP and imaging began to define RTCB's complex composition and nucleocytoplasmic shuttling, placing it in a transcription-dependent DDX1/FAM98B/hCLE assembly.

    Evidence Co-immunoprecipitation, subcellular fractionation, photoactivatable GFP imaging, transcription inhibition, and siRNA knockdown in human cells

    PMID:24608264

    Open questions at the time
    • Functional consequence of nuclear import not directly tested for RTCB
    • Stoichiometry and architecture of the complex undefined at this stage
  7. 2015 High

    Stepwise mutagenesis and substrate-bound structures assigned specific active-site residues to individual catalytic steps and revealed possible redox sensitivity.

    Evidence Alanine scanning of E. coli RtcB with step-resolved ligation assays; later crystal structure of RtcB bound to a 5'-OH oligonucleotide showing nucleophile and backbone contacts and an oxidized active-site cysteine

    PMID:26858100 PMID:33619169

    Open questions at the time
    • Redox regulation of the active-site cysteine inferred structurally, not demonstrated functionally
    • Mapping done on bacterial/archaeal orthologs
  8. 2015 High

    Genetic dissection in neurons uncovered ligase functions of RTCB independent of tRNA splicing and UPR, including a role inhibiting axon regeneration.

    Evidence C. elegans axon injury assays with epistasis against tRNA, UPR, and archease mutants, plus injury-site localization

    PMID:26100902

    Open questions at the time
    • The relevant RNA substrate in axon regeneration not identified
    • Archease-independent activation mechanism unexplained
  9. 2017 High

    Bacterial studies expanded RTCB-family substrate scope to ribosomal RNA, showing re-ligation of truncated 16S rRNA restores translation capacity.

    Evidence In vitro re-ligation of truncated 16S rRNA and in vivo ΔrtcB bacterial translation assays

    PMID:27789694

    Open questions at the time
    • Direct relevance to human RTCB rRNA repair not established
    • Specialized vs. canonical ribosome targeting in vivo not fully resolved
  10. 2022 Medium

    Post-translational regulation of RTCB was defined, showing Y306 phosphorylation tunes UPR signaling outcomes and deubiquitination controls protein stability.

    Evidence Phosphoproteomics, RTCB-IRE1α Co-IP, c-Abl/PTP1B perturbation with XBP1 splicing readouts; separate USP45 deubiquitination assays with proliferation/chemoresistance and tumor models; tiRNA re-ligation assays defining a tRNA-repair regulatory role

    PMID:35193953 PMID:36361884 PMID:41468936

    Open questions at the time
    • Structural impact of Y306 phosphorylation on the RTCB-IRE1α interface unknown
    • Whether USP45 and phospho-regulation intersect not tested
  11. 2022 High

    Metal-resolved structures and a ribosome-repair cryo-EM structure clarified how cofactor identity gates catalysis and how RtcB-family enzymes are targeted to specialized substrates.

    Evidence X-ray structures of RtcB-GTP with permissive (Mn/Co/Ni) and inhibitory (Zn/Cu) metals correlated to activity; cryo-EM of bacterial RtcB2-PrfH ribosome-repair complex

    PMID:35858322 PMID:36130078

    Open questions at the time
    • RtcB2/PrfH targeting is bacterial-specific; human substrate-targeting factors not yet defined
    • In vivo metal selectivity in human cells not measured
  12. 2024 High

    Cryo-EM of the human RTCB-Archease complex provided the mechanistic basis for activation, showing Archease coordinates GTP/metal and blocks futile substrate binding during the catalytic cycle.

    Evidence Cryo-EM of pre- and post-activation states with biochemical and structure-based mutagenesis of human proteins

    PMID:38493148

    Open questions at the time
    • Dynamics of Archease cycling on and off RTCB during turnover not resolved
    • How RNA substrate is admitted after activation incompletely defined
  13. 2025 High

    Atomic-resolution structure and Ashwin-NLS genetics defined the architecture and compartment-specific functional partitioning of RTCB complexes.

    Evidence Cryo-EM of the human tRNA-LC showing CGI-99/DDX1/FAM98B helical bundle and FAM98B-CGI-99 clamp on Ashwin; NLS mutagenesis and fractionation showing FAM98B/Ashwin complexes route to the nucleus for pre-tRNA splicing while FAM98A/C complexes stay cytoplasmic (preprints)

    PMID:bio_10.1101_2025.08.01.668163 PMID:bio_10.1101_2025.08.01.668197

    Open questions at the time
    • Functional roles of FAM98A/FAM98C-specific complexes not fully characterized
    • Preprint status; peer review pending
  14. 2025 Medium

    A spliceosome-independent 'SOS splicing' pathway revealed a new biological function: RTCB ligates mRNA fragments after DNA transposon excision via CAAP1 and AKAP17A.

    Evidence Genetic screens in C. elegans and human cells, RNA ligation assays, and epistasis with CAAP1 and AKAP17A (preprint)

    PMID:bio_10.1101_2025.02.14.638102

    Open questions at the time
    • Preprint without peer review
    • How TE-excision substrates are generated and recognized not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RTCB substrate selectivity and compartment-specific complex composition are coordinated in cells, and which non-canonical substrates dominate physiologically, remains open.
  • No unified model linking phospho/ubiquitin regulation to complex composition
  • Endogenous RNA substrate repertoire across compartments not comprehensively mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 6 GO:0003723 RNA binding 3 GO:0016874 ligase activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ARCHEASEASWCGI-99DDX1FAM98BIRE1ΑUSP45
Complex memberships
tRNA ligase complex (tRNA-LC)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 HSPC117 (RTCB) is the essential catalytic subunit of a human tRNA splicing ligase complex. Activity-guided purification from HeLa cell extracts identified HSPC117 as the RNA ligase responsible for direct exon ligation in tRNA splicing. RNAi-mediated depletion inhibited maturation of intron-containing pre-tRNA both in vitro and in living cells. Activity-guided purification from HeLa extracts, RNAi knockdown, in vitro and in vivo pre-tRNA maturation assays Science High 21311021
2011 E. coli RtcB is an RNA ligase that seals broken tRNA-like stem-loop structures with 2',3'-cyclic phosphate and 5'-OH ends to form a splice junction with a 2'-OH, 3',5'-phosphodiester, establishing RtcB as an RNA repair/splicing ligase. In vitro RNA ligase assay with purified E. coli RtcB on tRNA-like substrates The Journal of Biological Chemistry High 21224389
2011 RtcB executes a two-step ligation pathway: (1) intrinsic 2',3'-cyclic phosphodiesterase activity hydrolyzes the cyclic phosphate to a 3'-monophosphate; (2) GTP-dependent ligation joins the 3'-monophosphate to the 5'-OH end. Both activities require manganese and are abolished by active-site mutagenesis. RtcB forms a covalent enzyme-guanylate (RtcB-GMP) intermediate via a phosphoramidate bond. In vitro biochemical assays with purified RtcB, active-site mutagenesis, GTP dependence assays, hydroxylamine/acid sensitivity tests The Journal of Biological Chemistry High 22045815
2011 E. coli RtcB can complement growth of yeast trl1Δ cells lacking endogenous tRNA ligase, demonstrating it is sufficient for tRNA splicing in vivo. RtcB also complements HAC1 mRNA splicing during the unfolded protein response in yeast, establishing it as a bona fide RNA repair enzyme for both tRNA and mRNA substrates. Genetic complementation of yeast trl1Δ, in vivo tRNA splicing and HAC1 mRNA splicing assays The Journal of Biological Chemistry High 21757685
2012 RtcB executes a three-step ligation pathway: (i) His337 reacts with GTP to form a covalent RtcB-(histidinyl-N)-GMP intermediate; (ii) guanylate is transferred to the RNA 3'-phosphate to form a polynucleotide-(3')pp(5')G intermediate; (iii) the 5'-OH attacks the 3'-ppG end to form the splice junction. This mechanism is unique among known nucleic acid ligases. In vitro biochemical reconstitution, mass spectrometry identification of covalent intermediates, site-directed mutagenesis of His337 Proceedings of the National Academy of Sciences High 22474365
2012 The cyclic phosphodiesterase step of RtcB requires GTP and formation of the RtcB-GMP adduct, establishing that guanylylation precedes both the cyclic phosphodiesterase and 3'-phosphate ligase steps. Evidence supports Scheme 1 (direct 5'-OH attack on 3'-ppG) over Scheme 2 (recycling via cyclic phosphate). In vitro kinetic assays with RtcB, GTP analogs, isotopic labeling, detection of RNA(3')pp(5')G intermediate Nucleic Acids Research High 22730297
2012 Crystal structures of Pyrococcus horikoshii RtcB with Mn²⁺ alone (1.6 Å) and with covalently bound GMP (2.3 Å) reveal two Mn²⁺ ions at the active site, the geometry of guanylylation of His404, and sulfate ions indicating RNA phosphate backbone binding sites. Mutagenesis validates roles of key residues in Mn²⁺ binding, GMP binding, and each ligation step. X-ray crystallography (1.6 Å and 2.3 Å), site-directed mutagenesis, biochemical ligation assays Proceedings of the National Academy of Sciences High 22949672
2013 Three crystal structures of Pyrococcus horikoshii RtcB capture snapshots of the entire guanylylation pathway: pre-GTP binding state (single Mn1), GTP-bound state with GTPαS analog (Mn1 stabilizes transition state, Mn2 coordinates γ-phosphoryl), and covalent His404-GMP intermediate. RtcB uses a two-metal mechanism converged independently with classical ATP/Mg-dependent ligases. X-ray crystallography with GTPαS analog and covalent GMP intermediate, structural comparison Biochemistry High 23560983
2014 RtcB is the primary UPR RNA ligase responsible for joining XBP1 mRNA exons during ER stress in mammals. In RtcB knockout cells, XBP1 mRNA splicing is defective during ER stress; genetic rescue with wild-type but not ligase-dead RtcB restores splicing. In vitro splicing confirms that RNA ligase activity is directly required. RtcB knockout cell line, synthetic XBP1 splicing circuit, genetic rescue, in vitro splicing assay Molecular Cell High 25087875
2014 Archease, co-encoded with RtcB in a tRNA splicing operon, activates RtcB by accelerating RNA 3'-P guanylylation and ligation steps, altering NTP cofactor specificity (allowing ATP, dGTP, ITP in addition to GTP), and rescuing inactivating mutations in the guanine-binding pocket. Archease metal-binding residues are required for activation. Crystal structure of Archease at 1.4 Å reveals a conserved metal-binding tip. Biochemical RNA ligation assays with purified proteins, mutagenesis of RtcB and Archease, X-ray crystallography (1.4 Å), NTP specificity assays Nucleic Acids Research High 24435797
2014 C. elegans RtcB (RTCB-1) ligates xbp-1 mRNA during the IRE-1 branch of the UPR. Without RtcB, protein stress causes accumulation of unligated xbp-1 mRNA fragments, defective UPR, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves; defects can be bypassed by pre-spliced tRNA expression. Additional functions independent of tRNA maturation and UPR also exist. C. elegans rtcb mutants, in vivo xbp-1 splicing assays, pre-spliced tRNA rescue, lifespan assays EMBO Reports High 25366321
2014 C. elegans RTCB-1 protects dopaminergic neurons from α-synuclein-induced degeneration. The neuroprotective role requires the RNA ligase activity of RTCB-1 (ligase-dead mutant loses protection) and is mediated through XBP-1 mRNA splicing in the UPR pathway. C. elegans neuronal RNAi, ligase-dead mutant, xbp-1 mRNA splicing assay, DA neuron degeneration scoring Journal of Neuroscience High 25429148
2014 HSPC117 (RTCB) associates with DDX1 and FAM98B in a complex that shuttles between nucleus and cytoplasm. Nuclear import of hCLE, DDX1, HSPC117, and FAM98B requires active transcription. Silencing of hCLE downregulates nuclear and cytosolic accumulation of HSPC117, DDX1, and FAM98B. Co-immunoprecipitation, subcellular fractionation, photoactivatable GFP live imaging, transcription inhibition, siRNA knockdown PloS one Medium 24608264
2015 RtcB RNA ligation in neurons inhibits axon regeneration after nerve injury in C. elegans, independently of tRNA ligation, UPR, and the cofactor archease. RtcB is enriched at axon termini after nerve injury. C. elegans axon injury assays, genetic epistasis with tRNA/UPR mutants, archease mutants, RtcB localization by fluorescence imaging Proceedings of the National Academy of Sciences High 26100902
2015 Archease enables multiple-turnover RNA ligation by RtcB; without Archease, RtcB from Thermus thermophilus is a single-turnover enzyme. Archease from P. horikoshii can activate T. thermophilus RtcB despite low sequence identity, but coevolution of both proteins is required for full functional interaction. In vitro RNA ligation kinetics with purified RtcB and Archease from multiple organisms, turnover number measurements RNA High 26385509
2016 Alanine scanning of E. coli RtcB active site reveals distinct roles of metal-coordinating residues: Cys78 is essential for all steps; Asp75 (Mn2 ligand) is required for 3'-phosphate guanylylation but not cyclic phosphodiesterase; His281 (Mn1 ligand) is required for overall ligation but not preguanylylated substrate sealing. Arg189 is implicated in engaging the 5'-OH RNA end (R189A slows sealing 200-fold). Alanine mutagenesis of E. coli RtcB, in vitro stepwise ligation assays with 3'-P, 2',3'-cP, and 3'-ppG substrates Journal of Bacteriology High 26858100
2017 E. coli RNA ligase RtcB reverses MazF-induced ribosome heterogeneity by re-ligating the truncated 3'-terminus of 16S rRNA in specialized ribosomes, restoring their ability to translate canonical mRNAs. This was demonstrated both in vitro and in vivo. In vitro RtcB ligation of truncated 16S rRNA, in vivo bacterial assays with ΔrtcB strains, ribosome translation assays Nucleic Acids Research High 27789694
2019 hCLE/RTRAF-HSPC117-DDX1-FAM98B form a cap-binding complex in HEK293T cells. All four proteins bind cap analog-containing resins independently of eIF4E. The complex associates with mRNAs involved in translation, and hCLE silencing reduces mRNA translation. Cap resin pulldown, competition/elution experiments, co-immunoprecipitation, siRNA knockdown with translation assay Frontiers in Physiology Medium 30833903
2021 Crystal structure of Pyrococcus horikoshii RtcB in complex with a 5'-OH DNA oligonucleotide (2.7 Å) reveals enzymic contacts: Asn202 to terminal 5'-OH nucleophile; Arg238 to phosphates at positions 1-3; Arg190 and Gln194 to T2pG3 phosphate; Arg190 π-cation interaction with G3 nucleobase. Active site Cys98 is oxidized to cysteine sulfonic acid, suggesting potential redox regulation. X-ray crystallography (2.7 Å) of RtcB-oligonucleotide complex, structural analysis RNA High 33619169
2022 RtcB is tyrosine-phosphorylated by c-Abl kinase and dephosphorylated by PTP1B phosphatase. Phosphorylation at Y306 perturbs RtcB interaction with IRE1α, thereby attenuating XBP1 mRNA splicing and shifting IRE1α signaling outputs. This phosphorylation-dependent regulation determines whether cells mount adaptive or pro-death UPR responses. Phosphoproteomic identification of phospho-Y306, co-immunoprecipitation of RtcB-IRE1α, pharmacological inhibition/activation of c-Abl and PTP1B, XBP1 splicing assays Life Science Alliance High 35193953
2022 RTCB ligase complex (RTCB-LC) negatively regulates stress-induced tRNA cleavage (tiRNA production). Knockdown of RTCB increases stress-induced tiRNA levels; in vitro, RtcB repairs gel-purified tiRNAs back to full-length tRNAs. Under oxidative stress, inhibition of RTCB-LC amplifies tiRNA production. RTCB siRNA knockdown, in vitro tiRNA re-ligation assay with purified RtcB, tiRNA quantification under oxidative stress International Journal of Molecular Sciences Medium 36361884
2022 Crystal structures of Pyrococcus horikoshii RtcB with GTP and various divalent metals (Mn, Co, Ni permissive; Zn, Cu inhibitory) reveal that M2 coordination geometry determines metal cofactor activity: permissive metals show pentahedral coordination contacting β- and γ-phosphates, while inhibitory Zn/Cu adopt tetrahedral geometry contacting only γ-phosphate. His404 attack angle is closer to apical for permissive metals. X-ray crystallography of multiple RtcB-GTP-metal complexes, in vitro guanylylation assays RNA High 36130078
2022 A subset of bacterial RtcB (RtcB2) specifically repairs ribosomal damage in the decoding center of the 30S subunit but not damaged tRNAs. PrfH dismantles the damaged 70S ribosome to expose the repair site; cryo-EM structure (2.55 Å) shows PrfH specifically recognizes the cleaved 3'-terminal nucleotide. RtcB2-PrfH together reverse ribosome-specific ribotoxin damage in vivo. Cryo-EM (2.55 Å), in vitro peptide release and RNA repair assays, cell-based ribotoxin resistance assays Proceedings of the National Academy of Sciences High 35858322
2023 RTCB competes with DDX21 for binding to RNA helicase DDX1. This competitive interaction attenuates the DDX21-DDX1 association, which suppresses type I and type III interferon expression and downstream IFN-stimulated gene expression, thereby facilitating influenza A virus replication. Co-immunoprecipitation of RTCB-DDX1 and DDX21-DDX1, RTCB knockout/overexpression with IFN reporter assays, competitive binding experiments Journal of Immunology Medium 37556111
2024 Structural analysis of the human RTCB-Archease complex in pre- and post-activation states reveals that Archease reaches into the active site of RTCB to coordinate GTP and metal ions, promoting formation of the covalent RTCB-GMP intermediate. During activation, Archease prevents futile RNA substrate binding to RTCB. Cryo-EM, biochemical activation assays, structure-based mutagenesis Nature Communications High 38493148
2025 USP45 deubiquitinase stabilizes RTCB by directly removing polyubiquitin chains from RTCB. USP45-mediated DDX1 deubiquitination requires RTCB, but RTCB deubiquitination is DDX1-independent, revealing an asymmetric regulatory hierarchy. USP45-RTCB-DDX1 axis promotes tumor cell proliferation and chemoresistance. Co-immunoprecipitation, deubiquitination assays, RTCB/DDX1 knockdown with proliferation and chemoresistance readouts, murine tumor models International Journal of Biological Macromolecules Medium 41468936
2008 Murine FAAP (ortholog of human HSPC117/RTCB) facilitates vinculin-paxillin association, decreases paxillin-FAK interaction, inhibits ERK phosphorylation, and causes impaired cell spreading and restrained focal adhesion translocation when overexpressed in HeLa cells. Transfection of FAAP in HeLa cells, co-immunoprecipitation of vinculin-paxillin and paxillin-FAK, ERK phosphorylation assay, cell spreading and focal adhesion assays Frontiers in Bioscience Low 18508721
2025 Cryo-EM structure of the human tRNA ligase complex (tRNA-LC) reveals that CGI-99, DDX1, and FAM98B form an alpha-helical bundle contacting RTCB on the opposite side from the ligase active site. FAM98B and CGI-99 form a co-folded heterodimer that clamps Ashwin in a pincer-like structure. FAM98A and FAM98C support compositionally distinct RTCB-containing complexes that lack Ashwin, potentially with distinct cellular functions. Cryo-EM (atomic resolution), structure-based mutagenesis, interaction analysis bioRxivpreprint High bio_10.1101_2025.08.01.668197
2025 Ashwin (ASW), a vertebrate-specific subunit of the tRNA-LC, contains a dual nuclear localization signal (NLS) that acts as the nuclear import factor for the entire complex. Disruption of the NLS retains the tRNA-LC in the cytoplasm, impairing pre-tRNA splicing and causing accumulation of 5' tRNA fragments. FAM98B-containing (but not FAM98A- or FAM98C-containing) RTCB complexes associate with ASW for nuclear localization, while FAM98A/C complexes remain cytoplasmic for XBP1 mRNA splicing. NLS mutagenesis, subcellular fractionation, pre-tRNA splicing assays, 5' tRNA fragment accumulation, NLS-RTCB rescue in ASW-depleted cells bioRxivpreprint High bio_10.1101_2025.08.01.668163
2025 RTCB participates in a novel 'SOS splicing' pathway that excises DNA transposons from host mRNAs independently of the spliceosome. RTCB ligates mRNA fragments generated by TE excision, and this requires CAAP1 as a bridging factor between RTCB and the TE-mRNA binding protein AKAP17A. This pathway is conserved in both C. elegans and human cells. Genetic screens in C. elegans and human cells, RNA ligation assays, functional epistasis with AKAP17A and CAAP1, mRNA splicing readouts bioRxivpreprint Medium bio_10.1101_2025.02.14.638102

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 A synthetic biology approach identifies the mammalian UPR RNA ligase RtcB. Molecular cell 209 25087875
2011 HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science (New York, N.Y.) 207 21311021
2011 RtcB is the RNA ligase component of an Escherichia coli RNA repair operon. The Journal of biological chemistry 134 21224389
2014 The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO reports 133 25366321
2011 Novel mechanism of RNA repair by RtcB via sequential 2',3'-cyclic phosphodiesterase and 3'-Phosphate/5'-hydroxyl ligation reactions. The Journal of biological chemistry 95 22045815
2012 RNA ligase RtcB splices 3'-phosphate and 5'-OH ends via covalent RtcB-(histidinyl)-GMP and polynucleotide-(3')pp(5')G intermediates. Proceedings of the National Academy of Sciences of the United States of America 94 22474365
2011 RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo. The Journal of biological chemistry 92 21757685
2017 Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly. Theranostics 52 29187905
2014 hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel transcription-dependent shuttling RNA-transporting complex. PloS one 52 24608264
2017 The RNA ligase RtcB reverses MazF-induced ribosome heterogeneity in Escherichia coli. Nucleic acids research 51 27789694
2012 Structural and mechanistic insights into guanylylation of RNA-splicing ligase RtcB joining RNA between 3'-terminal phosphate and 5'-OH. Proceedings of the National Academy of Sciences of the United States of America 51 22949672
2020 Soy Isoflavone Genistein Impedes Cancer Stemness and Mesenchymal Transition in Head and Neck Cancer through Activating miR-34a/RTCB Axis. Nutrients 48 32610494
2014 RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded protein response pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 25429148
2012 The sequential 2',3'-cyclic phosphodiesterase and 3'-phosphate/5'-OH ligation steps of the RtcB RNA splicing pathway are GTP-dependent. Nucleic acids research 45 22730297
2013 Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation. Biochemistry 44 23560983
2014 A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation. Nucleic acids research 42 24435797
2013 2'-Phosphate cyclase activity of RtcA: a potential rationale for the operon organization of RtcA with an RNA repair ligase RtcB in Escherichia coli and other bacterial taxa. RNA (New York, N.Y.) 36 23945037
2015 RNA ligation in neurons by RtcB inhibits axon regeneration. Proceedings of the National Academy of Sciences of the United States of America 29 26100902
2022 RTCB Complex Regulates Stress-Induced tRNA Cleavage. International journal of molecular sciences 24 36361884
2019 hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation. Frontiers in physiology 20 30833903
2015 Coevolution of RtcB and Archease created a multiple-turnover RNA ligase. RNA (New York, N.Y.) 20 26385509
2017 Site-Selective RNA Splicing Nanozyme: DNAzyme and RtcB Conjugates on a Gold Nanoparticle. ACS chemical biology 16 29155548
2022 Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs. Life science alliance 15 35193953
2020 lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer. OncoTargets and therapy 15 32273717
2022 Sequential rescue and repair of stalled and damaged ribosome by bacterial PrfH and RtcB. Proceedings of the National Academy of Sciences of the United States of America 14 35858322
2021 Structure of 3'-PO4/5'-OH RNA ligase RtcB in complex with a 5'-OH oligonucleotide. RNA (New York, N.Y.) 14 33619169
2016 Distinct Contributions of Enzymic Functional Groups to the 2',3'-Cyclic Phosphodiesterase, 3'-Phosphate Guanylylation, and 3'-ppG/5'-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway. Journal of bacteriology 14 26858100
2010 HSPC117 deficiency in cloned embryos causes placental abnormality and fetal death. Biochemical and biophysical research communications 14 20510672
2021 Protein Aggregation Patterns Inform about Breast Cancer Response to Antiestrogens and Reveal the RNA Ligase RTCB as Mediator of Acquired Tamoxifen Resistance. Cancers 13 34206811
2019 The bacterial RNA ligase RtcB accelerates the repair process of fragmented rRNA upon releasing the antibiotic stress. Science China. Life sciences 13 31250189
2017 Homology model of the human tRNA splicing ligase RtcB. Proteins 13 28707320
2021 Putative RNA Ligase RtcB Affects the Switch between T6SS and T3SS in Pseudomonas aeruginosa. International journal of molecular sciences 10 34830443
2008 FAAP, a novel murine protein, is involved in cell adhesion through regulating vinculin-paxillin association. Frontiers in bioscience : a journal and virtual library 10 18508721
2017 Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP. Proteins 8 28656626
2014 Making ends meet: a role of RNA ligase RTCB in unfolded protein response. The EMBO journal 8 25404664
2010 Expression and regulation of FAAP in the mouse epididymis. Endocrine 8 21046479
2024 Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease. Nature communications 7 38493148
2022 Structures of RNA ligase RtcB in complexes with divalent cations and GTP. RNA (New York, N.Y.) 7 36130078
2023 Insights into the structure and function of the RNA ligase RtcB. Cellular and molecular life sciences : CMLS 6 37935993
2024 Multiscale In Silico Study of the Mechanism of Activation of the RtcB Ligase by the PTP1B Phosphatase. Journal of chemical information and modeling 5 38282538
2023 The RNA-Splicing Ligase RTCB Promotes Influenza A Virus Replication by Suppressing Innate Immunity via Interaction with RNA Helicase DDX1. Journal of immunology (Baltimore, Md. : 1950) 5 37556111
2021 YY1 and RTCB in mouse uterine decidualization and embryo implantation. Reproduction (Cambridge, England) 5 34591784
2019 Expression and subcellular localization of HSPC117 in min pig tissues and the PK15 cell line. Technology and health care : official journal of the European Society for Engineering and Medicine 3 31045548
2014 HSPC117 is regulated by epigenetic modification and is involved in the migration of JEG-3 cells. International journal of molecular sciences 3 24941254
2022 High-throughput mapping of RNA solvent accessibility at the single-nucleotide resolution by RtcB ligation between a fixed 5'-OH-end linker and unique 3'-P-end fragments from hydroxyl radical cleavage. RNA biology 2 36369947
2020 lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer [Retraction]. OncoTargets and therapy 2 32848416
2025 Deubiquitinase USP45 stabilizes RTCB and DDX1, promoting tumorigenesis and chemoresistance. International journal of biological macromolecules 1 41468936
2024 RTCB deficiency triggers colitis in mice by influencing the NF-κB and Wnt/β-catenin signaling pathways. Acta biochimica et biophysica Sinica 1 38425245
2021 Biomimetic amphiphilic FAAP NPs nanoparticles: Synthesis, characterization and antivirus activity. International immunopharmacology 1 34619499
2026 RTCB is essential for early mouse embryogenesis. Biology of reproduction 0 41524728
2022 Application of RtcB ligase to monitor self-cleaving ribozyme activity by RNA-seq. Biological chemistry 0 35025187
2019 Purification and enzymatic characterization of the RNA ligase RTCB from Thermus thermophilus. Biotechnology letters 0 31280403

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