ATP-dependent DNA/RNA helicase DHX36

UniProt Q9H2U1 Organism Homo sapiens Gene DDX36, DHX36, KIAA1488, MLEL1, RHAU EC 3.6.4.12, 3.6.4.13

Also known as: DDX36, DHX36, KIAA1488, MLEL1, RHAU

Function

Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures. Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses. G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-DNA and G4-RNA). Plays a role in genomic integrity. Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription. Plays a role in transcriptional regulation. Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression. Plays a role in post-transcriptional regulation. Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage. Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability. Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression. Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively. Also binds to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation. Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay. Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). Required for early embryonic development and hematopoiesis. Involved in the regulation of cardioblast differentiation and proliferation during heart development. Involved in spermatogonia differentiation. May play a role in ossification (By similarity).

Classification

Family (Pfam): PF00270 DEAD, PF21010 HA2_C, PF00271 Helicase_C, PF07717 OB_NTP_bind, PF26026 RNA_hel_CTD, PF04408 WHD_HA2
InterPro: DEAD-box_helicase_OB_fold, DEAD/DEAH_box_helicase_dom, DNA/RNA_helicase_DEAH_CS, HA2_WH, Helicase-assoc_dom, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, RNA_hel_CTD
Functional cluster: Protein Serine/Threonine Kinases

Experimental structures · PDB · 3

2N16 NMR
2N21 NMR
6Q6R X-ray 1.50A

A predicted model is available from AlphaFold.

Gene Ontology · 62

Neighborhood · nearest proteins

Nearest neighbours of ATP-dependent DNA/RNA helicase DHX36: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

ATP-dependent DNA/RNA helicase DHX36 2 shared papers
H/ACA ribonucleoprotein complex subunit DKC1 1 shared papers
Telomerase reverse transcriptase 1 shared papers
Probable ATP-dependent RNA helicase DDX5 3 shared papers
Probable ATP-dependent RNA helicase DDX17 2 shared papers
Interleukin enhancer-binding factor 3 2 shared papers
ELAV-like protein 1 2 shared papers
Poly(A)-specific ribonuclease PARN 1 shared papers
Exosome complex component RRP40 1 shared papers
Exosome complex component 10 1 shared papers
Histone deacetylase 3 1 shared papers
ATP-dependent RNA helicase DHX30 1 shared papers

Literature · 30 cited papers

The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3'-End Processing Following UV-Induced DNA Damage. J. Mol. Biol. · 2017
Biophysical Characterization of G-Quadruplex Recognition in the PITX1 mRNA by the Specificity Domain of the Helicase RHAU. PLoS ONE · 2015
Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development. Cell Rep. · 2015
Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex. Proc. Natl. Acad. Sci. U.S.A. · 2015
Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE · 2015
Biochemical characterization of G4 quadruplex telomerase RNA unwinding by the RNA helicase RHAU. Methods Mol. Biol. · 2015
The RNA helicase RHAU (DHX36) suppresses expression of the transcription factor PITX1. Nucleic Acids Res. · 2014
Binding of G-quadruplexes to the N-terminal recognition domain of the RNA helicase associated with AU-rich element (RHAU). J. Biol. Chem. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary. Nucleic Acids Res. · 2012
Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1. Nucleic Acids Res. · 2012
The DEAH-box RNA helicase RHAU binds an intramolecular RNA G-quadruplex in TERC and associates with telomerase holoenzyme. Nucleic Acids Res. · 2011
… and 18 more in the literature graph

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