| 2009 |
Wrap53 (antisense transcript) regulates endogenous p53 mRNA levels and is required for p53 induction upon DNA damage by targeting the 5' UTR of p53 mRNA; blocking potential Wrap53/p53 RNA hybrids reduces p53 levels, demonstrating regulation via direct RNA-RNA interaction. |
siRNA knockdown, overexpression, blocking of RNA hybrids, RT-PCR/immunoblot |
Molecular cell |
High |
19250907
|
| 2010 |
WRAP53 protein (WDR79/TCAB1) is essential for Cajal body maintenance and formation; it associates with coilin, SMN, and importin-β, mediates SMN-coilin and SMN-importin-β complex formation, and is required for nuclear import and Cajal body targeting of the SMN complex. |
RNAi knockdown, immunofluorescence, co-immunoprecipitation |
PLoS biology |
High |
21072240
|
| 2011 |
Disruption of TCAB1 (WRAP53β) by missense mutations in dyskeratosis congenita patients misdirects telomerase RNA (hTR) from Cajal bodies to nucleoli, preventing telomerase from elongating telomeres. |
Patient mutation identification, cellular localization assays (fluorescence imaging), telomere length analysis |
Genes & development |
High |
21205863
|
| 2011 |
WRAP53 protein knockdown triggers apoptosis through the mitochondrial pathway (Bax/Bak activation, loss of mitochondrial membrane potential, cytochrome c release), demonstrating WRAP53 protein is required for cancer cell survival via mitochondrial apoptosis suppression. |
siRNA knockdown, flow cytometry, Bax/Bak activation assay, mitochondrial membrane potential assay, cytochrome c release, Bcl-2 rescue |
Cell death & disease |
Medium |
21368886
|
| 2012 |
TCAB1 is required for telomerase recruitment to telomeres independently of Cajal body integrity; TCAB1 itself localizes to telomeres in a telomerase-dependent but Cajal body-independent manner, demonstrating a direct transport role for TCAB1 beyond Cajal body scaffolding. |
Coilin depletion (genetic), TCAB1 knockdown, telomerase overexpression rescue assays, fluorescence localization, hTERT point mutation analysis |
Molecular and cellular biology |
High |
22547674
|
| 2012 |
WDR79 (WRAP53β) binds CAB boxes (UGAG motifs) in the 3' hairpin of intron-encoded AluACA RNAs in a cumulative fashion; AluACA RNPs associate with H/ACA core proteins and accumulate in the nucleoplasm rather than Cajal bodies. |
Co-immunoprecipitation, RNA co-IP, mutation analysis of CAB boxes, cellular fractionation/fluorescence |
Genes & development |
Medium |
22892240
|
| 2014 |
CTCF binds Wrap53 RNA directly through a dedicated RNA-binding region (RBR) distinct from its DNA-binding domain; this interaction regulates p53 expression. Depletion of CTCF reduces Wrap53 RNA levels, and a CTCF RBR mutant causes a defective p53 DNA damage response. |
PAR-CLIP-seq, CTCF depletion, RBR mutagenesis, reporter assays, immunoprecipitation |
Genes & development |
High |
24696455
|
| 2014 |
The chaperonin CCT/TRiC is required for proper folding of TCAB1; TRiC depletion causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. DC patient-derived mutations in TCAB1 impair TRiC-mediated folding. |
Genome-wide siRNA screen (high-content imaging), TRiC depletion, co-immunoprecipitation, telomere elongation assay, patient mutation functional analysis |
Cell |
High |
25467444
|
| 2016 |
Minimized hTR (binding sites for TERT only) maintains telomeres even in TCAB1 knockout or Coilin knockout cells, demonstrating that TCAB1 and Cajal bodies are dispensable for telomere maintenance when TERT is overexpressed, but wild-type hTR shows distinct changes in telomerase action without TCAB1. |
CRISPR knockout (TCAB1, Coilin), minimized hTR expression, telomere length and elongation assays |
eLife |
High |
27525486
|
| 2017 |
WDR79 (WRAP53β) colocalized and physically interacted with USP7 in the nucleus of NSCLC cells; this interaction reduced ubiquitination of Mdm2 and p53, increasing their stability and extending their half-life, thereby promoting cell proliferation via the Mdm2-p53 pathway. |
Co-immunoprecipitation, co-localization (immunofluorescence), ubiquitination assays, USP7 knockdown, half-life measurement |
Cell death & disease |
Medium |
28406480
|
| 2017 |
WDR79 (WRAP53β) physically interacts with and stabilizes UHRF1 in the nucleus by protecting it from poly-ubiquitination-mediated proteolysis, thereby promoting NSCLC cell proliferation. |
Co-immunoprecipitation, co-localization, ubiquitination assay, WDR79 knockdown/overexpression, rescue experiments |
Journal of cellular and molecular medicine |
Medium |
29516630
|
| 2017 |
WDR79/TCAB1 depletion in Drosophila and C. elegans causes locomotion defects similar to SMN depletion; SMN overexpression rescues WDR79 loss-of-function phenotype in flies, and WDR79 overexpression ameliorates locomotion defects from SMN depletion, demonstrating cooperative, evolutionarily conserved function in the nervous system. |
Genetic epistasis (overexpression rescue), locomotion assays in Drosophila and C. elegans, RNAi/genetic depletion |
Neurobiology of disease |
Medium |
28502804
|
| 2018 |
TCAB1 controls the conformation of the CR4/5 domain of hTR; loss of TCAB1 causes unfolding of CR4/5 helices required for catalysis and TERT association, reducing telomerase catalytic activity without affecting enzyme assembly, revealing a conformational 'activity switch' in telomerase RNA. |
TCAB1 knockout/depletion, RNA structural probing, telomerase activity assay, hTR-TERT association assay, CR4/5 mutagenesis |
Cell |
High |
29804836
|
| 2020 |
Biallelic WRAP53β mutations (L283F, R398W) in a HHS patient cause destabilization, mislocalization, and faulty interactions of WRAP53β due to misfolding by the TRiC chaperonin; these mutants cannot elongate telomeres, maintain Cajal bodies, or repair DNA double-strand breaks. |
Patient mutation characterization, protein stability/localization assays, TRiC interaction assays, telomere elongation assay, DNA DSB repair assay |
Cell death & disease |
Medium |
32303682
|
| 2020 |
Oxygen/glucose deprivation triggers reactive oxygen species that induce DNA double-strand breaks and cause WRAP53 to translocate to the nucleus in neurons, where it promotes DSB repair; this was confirmed in a mouse model of stroke. |
OGD neuronal model, ROS measurement, live-cell imaging of WRAP53 translocation, DSB repair assays, in vivo mouse stroke model |
Science advances |
Medium |
33028529
|
| 2021 |
TCAB1 knockdown induces cellular senescence in cancer cells by reducing proteasomal degradation of p21 via regulation of p21 ubiquitination, without affecting p21 mRNA levels; restoring p21 depletion or TCAB1 re-expression rescues the senescence phenotype. |
siRNA knockdown, SA-β-galactosidase staining, immunoprecipitation ubiquitination assay, qRT-PCR/western blot, rescue experiments |
Cancer cell international |
Medium |
33413389
|
| 2023 |
In the absence of TCAB1, a large fraction of telomerase RNA (TR) is tightly bound to the nucleolus while TERT is largely excluded from the nucleolus, reducing telomerase assembly; TCAB1 retains TR in the nucleoplasm to prevent sequestration in the nucleolus and enable TERT-TR assembly. |
TCAB1 knockout, cellular fractionation, fluorescence imaging, telomerase assembly assays |
Cell reports |
Medium |
37267110
|
| 2025 |
ALKBH5-mediated m6A demethylation of 5' uncapped and polyadenylated WRAP53 transcripts decreases WRAP53 stability and translation efficiency; reduced WRAP53 disrupts the interaction between USP6 and RALBP1, promoting RALBP1 degradation and suppressing PI3K/Akt/mTOR signaling. |
m6A modification mapping, ALKBH5 knockdown/overexpression, WRAP53 stability/translation assays, Co-IP (USP6-RALBP1), pathway signaling assays |
Molecular cancer |
Medium |
39815301
|