| 2002 |
Yeast Shq1p (SHQ1 ortholog) is required for stability of box H/ACA snoRNAs; depletion causes dramatic decrease in H/ACA snoRNA levels and ribosomal RNA processing defects. Shq1p localizes to the nucleus and interacts with H/ACA core proteins Nhp2p and Cbf5p (NAP57/dyskerin ortholog). Shq1p and Naf1p form a complex but are not strongly associated with mature snoRNPs, placing them in early biogenesis steps. |
Yeast depletion strains, in vivo co-immunoprecipitation, nuclear localization assay |
The Journal of biological chemistry |
High |
12228251
|
| 2008 |
The N-terminal CS (HSP20-like) domain of yeast Shq1p adopts an anti-parallel β-sandwich fold. Deletion or point mutations (F6, Q10, K80) in the CS domain destabilize Shq1p in vivo, cause temperature-sensitive growth, and deplete H/ACA snoRNAs with rRNA processing defects, establishing the CS domain as essential for H/ACA snoRNP biogenesis. No interaction was detected between the Shq1p CS domain and yeast Hsp90 in vitro. |
Crystal structure determination, deletion analysis, in vivo point mutagenesis, in vitro pulldown with Hsp90 (negative) |
The Journal of biological chemistry |
High |
19019820
|
| 2009 |
Human SHQ1 binds NAP57/dyskerin (the major H/ACA core pseudouridine synthase) in vivo and in vitro, and this interaction precludes binding of NAF1 and other H/ACA core proteins. SHQ1 acts before NAF1 in the assembly pathway. SHQ1 localizes to the nucleoplasm and is excluded from nucleoli and Cajal bodies (sites of mature H/ACA RNPs). Knockdown of SHQ1 prevents accumulation of newly synthesized H/ACA reporter RNA and reduces endogenous H/ACA RNA levels including telomerase RNA. Excess recombinant SHQ1 interferes with NAF1-dependent in vitro assembly of functional H/ACA RNPs. The N-terminal CS domain of SHQ1 is dispensable for NAP57 binding. |
In vivo and in vitro co-immunoprecipitation/pulldown, siRNA knockdown, immunofluorescence localization, in vitro H/ACA RNP assembly assay with recombinant SHQ1 |
RNA (New York, N.Y.) |
High |
19383767
|
| 2009 |
Yeast Shq1p binds the pseudouridylating enzyme Cbf5p through its C-terminal domain (with synergy from the N-terminal domain). The NMR solution structure of the N-terminal domain is homologous to the 'Chord and Sgt1' (CS) domain of Hsp90 co-chaperones, yet Shq1p does not interact with yeast Hsp90 in vitro. Shq1p has stand-alone chaperone activity in vitro, harbored mainly by the C-terminal domain but enhanced by the N-terminal domain. |
NMR structure determination, in vitro binding assays, in vitro chaperone activity assay |
Journal of molecular biology |
High |
19426738
|
| 2011 |
Crystal structure of the C-terminal SHQ1-specific domain (SSD) of yeast Shq1p in complex with the RNA-binding domain of Cbf5p (lacking catalytic domain) shows that SSD uses the RNA-protein-binding sites of Cbf5p via structural mimicry of H/ACA RNA, functioning as an RNA placeholder/chaperone that prevents Cbf5p from non-specific RNA binding before H/ACA RNP assembly. Mutations causing X-linked dyskeratosis congenita modulate this SHQ1-dyskerin interaction. |
Crystal structure determination of Shq1p SSD–Cbf5p complex, structure-based functional inference validated by mutational analysis |
Genes & development |
High |
22085966
|
| 2011 |
Crystal structure of yeast Shq1 SSD alone and in complex with Cbf5p, Nop10, and Gar1 reveals that SSD adopts a novel helical fold and contacts the PUA domain and disordered C-terminal extension (CTE) of Cbf5p. Shq1 binds Cbf5p independently of H/ACA RNP proteins Nop10, Gar1, Nhp2, and assembly factor Naf1, but shares an overlapping binding surface with H/ACA RNA. Dyskeratosis congenita mutations in the Cbf5p CTE likely interfere with Shq1 binding. Shq1 point mutations disrupting Cbf5 interaction suppress yeast growth, especially at elevated temperatures. |
Crystal structure determination, in vitro binding assays, yeast growth assays with point mutants |
The EMBO journal |
High |
22117216
|
| 2014 |
Crystal and NMR structures of the human SHQ1 CS domain (hCS) show an immunoglobulin-like β-sandwich fold similar to yeast CS. NMR chemical shift perturbation (CSP) experiments with peptides from Cbf5/dyskerin identified a conserved surface on the CS domain important for Cbf5/dyskerin binding, allowing construction of a HADDOCK docking model of the full SHQ1–Cbf5 pre-H/ACA RNP complex. |
Crystal structure, NMR structure determination, NMR chemical shift perturbation assays, HADDOCK computational docking |
Journal of molecular biology |
High |
25553844
|
| 2017 |
Two compound heterozygous mutations in SHQ1 (identified by exome sequencing) map to the SHQ1–NAP57 interface and impair interaction of recombinant SHQ1 variants with NAP57 in pulldown assays, demonstrating that SHQ1 mutations cause disease by disrupting its chaperone interaction with dyskerin/NAP57. |
Exome sequencing, recombinant protein pulldown assays |
Molecular genetics & genomic medicine |
Medium |
29178645
|
| 2018 |
In T-ALL cells, oncogenic NOTCH1 directly binds the SHQ1 promoter and activates its transcription. SHQ1 depletion impairs widespread RNA splicing and prominently downregulates MYC through inefficient splicing. MYC overexpression rescues T-ALL cell death caused by SHQ1 inactivation, placing SHQ1 in a NOTCH1→SHQ1→MYC splicing axis required for T-ALL survival. |
ChIP (NOTCH1 at SHQ1 promoter), shRNA/siRNA knockdown, RNA-Seq splicing analysis, rescue by MYC overexpression, murine T-ALL xenograft model |
Nature communications |
High |
30323192
|
| 2020 |
SHQ1 is regulated as an ER stress response gene by p50ATF6 and XBP1s acting through an ER-stress-response-like element on the SHQ1 promoter. SHQ1 interacts with the ER chaperone GRP78 and, upon binding, releases ER sensors PERK/IRE1α/ATF6 from GRP78 complexes, leading to hyper-activation of the unfolded protein response (UPR) and apoptosis under persistent ER stress. |
Promoter reporter assays, co-immunoprecipitation (SHQ1–GRP78), western blot of UPR sensors, HCC xenograft model with SHQ1 restoration |
Cell death & disease |
Medium |
32522979
|
| 2023 |
Human SHQ1 variants R335C and A426V expressed in a conditional yeast strain progressively depleted of endogenous Shq1 fail to maintain H/ACA snoRNA levels and cause accumulation of unprocessed pre-rRNAs and reduced ribosome production. Immunoprecipitation showed that interaction of Cbf5 (dyskerin ortholog) with SHQ1 variants was weakened but not abolished; yeast two-hybrid confirmed R335C is more deleterious than A426V. Wild-type human SHQ1 complements the Shq1-depleted yeast strain. |
Conditional yeast depletion strain complementation, northern blot for snoRNAs and pre-rRNAs, polysome/ribosome profiling, co-immunoprecipitation, yeast two-hybrid |
Frontiers in genetics |
Medium |
37818102
|
| 2024 |
SHQ1 knockdown in cortical neurons impairs neuronal migration and neurite morphology in vivo (in utero electroporation) and neurite growth and glutamate sensitivity in vitro. Co-immunoprecipitation confirmed SHQ1 interacts with DKC1 (dyskerin), and most pathogenic SHQ1 variants attenuate this interaction. SHQ1 knockdown also increases dopaminergic pathway activity, potentially underlying enhanced glutamate toxicity. |
shRNA knockdown, in utero electroporation, co-immunoprecipitation (SHQ1–DKC1), neuronal morphology quantification, dopaminergic function assay |
Experimental neurology |
Medium |
39326821
|
| 2025 |
VIRMA-mediated m6A modification of SHQ1 mRNA stabilizes it via the m6A reader HNRNPA2B1; Virma knockout reduces m6A on Shq1 mRNA, decreases HNRNPA2B1 binding, lowers Shq1 mRNA stability and protein levels, and impairs PI3K/AKT signaling and cell proliferation in liver regeneration. Shq1 supplementation rescues the liver regeneration defect caused by Virma deficiency. |
MeRIP-seq (m6A mapping), liver-specific Virma knockout (Cre-loxP), RIP assay (HNRNPA2B1–Shq1 mRNA), mRNA stability assay, in vivo rescue with Shq1, AKT inhibitor experiments |
Acta pharmaceutica Sinica. B |
Medium |
41132854
|
| 2025 |
Wild-type SHQ1 enhances caspase-3 cleavage, TUNEL signals, ER stress proteins, and ROS production in SH-SY5Y neuroblastoma cells, leading to apoptosis. Three neurodevelopmental SHQ1 variants (Y65X, V271E, L333V) attenuate apoptosis, ER stress protein expression, and ROS production compared to wild-type. Despite functional differences, binding of SHQ1 variants to GRP78 remains unchanged, dissociating GRP78 binding from the apoptotic/ER-stress function. |
Transfection of WT and variant SHQ1 in SH-SY5Y cells, caspase-3 cleavage assay, TUNEL, western blot for ER stress markers, ROS measurement, co-immunoprecipitation (SHQ1–GRP78) |
Neuroscience |
Medium |
40967470
|