| 2015 |
The DEAH-box helicase Dhr1 (yeast ortholog of DHX37) is responsible for displacing U3 snoRNA from the pre-ribosome. An active-site mutant of Dhr1 blocked U3 release, trapping a pre-40S particle containing U3, pre-rRNA, and early-acting assembly factors but lacking ribosomal proteins surrounding the central pseudoknot. In vivo crosslinking showed Dhr1 contacts pre-rRNA and U3 sequences flanking regions that base-pair to form the central pseudoknot. Point mutations in the U3 box A region suppressed a cold-sensitive Dhr1 mutation, indicating U3 is an in vivo substrate. Dhr1 was also shown to unwind U3-18S duplexes in vitro. |
Active-site mutagenesis, in vivo crosslinking (CRAC), genetic suppressor analysis, in vitro unwinding assay |
PLoS biology |
High |
25710520
|
| 2016 |
Utp14 recruits and activates Dhr1 (yeast DHX37 ortholog) at the preribosome. Utp14 forms a complex with Dhr1 and directly stimulates its RNA-unwinding activity in vitro. Mutations in a discrete region of Utp14 reduced Dhr1 interaction and phenocopied a helicase-inactive Dhr1 mutant (accumulation of Dhr1 and U3 in a pre-40S particle). Stable association of Dhr1 with the preribosome requires both Utp14 and Bud23, revealing that Utp14 is bifunctional: it recruits Dhr1 (together with Bud23) and activates its unwinding activity. |
In vitro unwinding stimulation assay, co-immunoprecipitation, genetic epistasis with bud23 and utp14 mutants |
Molecular and cellular biology |
High |
26729466
|
| 2018 |
Human DHX37 is required for maturation of the small ribosomal subunit. In vivo crosslinking showed DHX37 binds directly to U3 snoRNA, and its catalytic activity is required for dissociation of U3 snoRNA from pre-ribosomal complexes, enabling central pseudoknot formation. Failure to recruit DHX37 to early pre-ribosomal particles triggers a quality-control pathway leading to pre-rRNA degradation. UTP14A was identified as a direct interaction partner of DHX37 that acts as a cofactor stimulating helicase activity in the context of U3 snoRNA release. |
In vivo UV crosslinking (CRAC), catalytic-dead mutant analysis, co-immunoprecipitation, siRNA knockdown with pre-rRNA processing readout |
RNA biology |
High |
30582406
|
| 2019 |
Crystal structure of human DHX37 in complex with single-stranded RNA was solved, revealing a canonical DEAH ATPase/helicase architecture and a structurally unique carboxy-terminal domain (CTD). Structural comparisons with ATP-analog-bound DEAH helicases suggest ATP-dependent 3'-to-5' RNA translocation via a register shift in bound RNA. A conserved sequence motif in UTP14A directly interacts with DHX37, stimulating its ATPase activity and enhancing RNA binding. The CTD of DHX37 is required (but not sufficient) for interaction with UTP14A in vitro and is essential for ribosome biogenesis in vivo. |
X-ray crystallography, in vitro ATPase assay, mutagenesis, pulldown/interaction mapping |
RNA (New York, N.Y.) |
High |
30910870
|
| 2019 |
The crystal structure of the yeast Dhr1 helicase module was solved, revealing a remarkable carboxy-terminal domain (CTD) essential for Dhr1 function in ribosome biogenesis in vivo and important for interaction with its coactivator Utp14 in vitro. DHX37 patient mutations (associated with microcephaly and neurological disease) mapped to this structure show functional consequences on ribosome biogenesis. |
X-ray crystallography, in vivo functional rescue assays, in vitro interaction assay |
Nucleic acids research |
High |
31188444
|
| 2022 |
Purified Dhr1 (yeast DHX37 ortholog) is an active RNA-dependent ATPase with specific RNA-unwinding activity in vitro. The N-terminus and an internal loop within the RecA2 domain are autoinhibitory elements. Utp14 can activate the ATPase activity of Dhr1 lacking the autoinhibitory N-terminal loop but not full-length Dhr1, and Utp14 activates Dhr1 by binding to the surface of the RecA1 and RecA2 domains rather than by displacing the inhibitory loop, which is distinct from G-patch protein activation of other DEXH/RHA helicases. |
In vitro ATPase assay, unwinding assay, mutagenesis, yeast genetics |
Methods in enzymology |
Medium |
35965019
|
| 2025 |
Dhr1 N-terminus and an internal loop within the RecA2 domain are autoinhibitory. Utp14 activates Dhr1 by binding to the surface of the RecA1 and RecA2 domains, a mechanism distinct from how G-patch proteins activate other DEXH/RHA helicases. Utp14 activates Dhr1 lacking the autoinhibitory N-terminal loop but not full-length Dhr1, suggesting Utp14 does not relieve autoinhibition by displacing the inhibitory loop. |
In vitro ATPase assay, unwinding assay, mutant analysis, yeast genetic complementation |
The Journal of biological chemistry |
Medium |
40024476
|
| 2022 |
DHX37 interacts with PLRG1 and co-occupies the promoter and superenhancer elements of cyclin D1 (CCND1) to transcriptionally activate CCND1 expression in hepatocellular carcinoma cells, promoting cell proliferation. This represents a non-canonical function of DHX37 distinct from its role in ribosome biogenesis. |
Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), epigenomic profiling, knockdown with proliferation assay |
Cancer research |
Medium |
35290436
|
| 2025 |
DHX37 (also annotated as DDX37) and DDX50 resolve RNA-DNA hybrids (R-loops) that form during transcription, thereby preventing replication stress and DNA damage. Depletion of DHX37 caused increased H2AX phosphorylation, increased comet tail length, decreased replication track length, and RPA focus formation. The increased RNA-DNA hybrids upon DHX37 depletion could be reversed by RNase H1 overexpression, and transcription inhibition prevented R-loop accumulation and DNA damage. |
siRNA knockdown, γH2AX immunofluorescence, comet assay, DNA fiber assay, RPA focus formation, RNase H1 rescue, RNA-DNA hybrid immunofluorescence |
Journal of molecular biology |
Medium |
40043837
|
| 2025 |
In an in vitro cellular model of human Sertoli cell formation, mutant DHX37 (p.R674Q) retains ATPase activity and is not associated with stabilization of cellular β-catenin. Transfection of mutant DHX37 in induced Sertoli-like cells (iSLCs) showed reduced activation of pro-testis genes compared to WT. HyperTRIBE combined with single-cell full-length RNA-sequencing revealed that WT DHX37 targets transcripts associated primarily with cytoskeleton organization, while the mutant DHX37 targets additional transcripts associated with protein degradation and cell death. |
ATPase activity assay, HyperTRIBE RNA-binding mapping, single-cell full-length RNA-seq, transfection in iSLCs |
bioRxivpreprint |
Medium |
bio_10.1101_2025.01.10.632330
|
| 2026 |
Cell-specific Dhx37 knockout in mouse Sertoli cells caused reduced testicular volume, lower testosterone levels, seminiferous tubule vacuolization, reduced cell proliferation, and elevated apoptosis. RIP-seq and RNAi-RNA-seq in Sertoli cells showed Dhx37 safeguards nucleolar integrity and PI3K-AKT signaling, and suppresses p53-driven apoptosis; Dhx37 loss triggers pro-apoptotic splicing. Loss of nucleolar integrity caused FBL to exit the nucleolus and bind MDM2, thereby releasing p53 to promote apoptosis. |
Conditional knockout mouse, immunofluorescence, single-nucleus RNA-seq, RIP-seq, RNAi-RNA-seq, Western blotting, qRT-PCR |
Cell death discovery |
Medium |
41535247
|
| 2024 |
A novel pathogenic DHX37 variant (p.Arg671Thr) found in a 46,XY DSD patient had no significant effect on intracellular localization of the DHX37 protein but significantly reduced its expression level in vitro, as assessed by immunofluorescence and Western blotting. |
Immunofluorescence (subcellular localization), Western blotting (protein level) |
Molecular genetics & genomic medicine |
Low |
38769888
|