Dhx36
Developmental stage
Expressed in the embryonic heart at 10.5 and increases from 14.5 to 16.5 dpc, and then gradually decreases until postnal day 7 (PubMed:26489465). Expressed during the testicular development from embryonic day 18.5 to postnatal day 35 (PubMed:25611385).
Domain
The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity).
Function
Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:25611385). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:21590736, PubMed:21703541). 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) (By similarity). Plays a role in genomic integrity (By similarity). 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 (By similarity). 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 (By similarity) (PubMed:25611385). Plays a role in post-transcriptional regulation (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Binds also to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (By similarity). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (By similarity). 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 (PubMed:21703541). Required for the early embryonic development and hematopoiesis (PubMed:22422825). Involved in the regulation of cardioblast differentiation and proliferation during heart development (PubMed:26489465). Involved in spermatogonia differentiation (PubMed:25611385). May play a role in ossification (PubMed:21590736).
Sequence Similarities
Belongs to the DEAD box helicase family. DEAH subfamily.
Tissue Specificity
Expressed in spermatogonia stem cells and primary spermatocytes (at protein level) (PubMed:25611385). Expressed strongly in testis. Weakly expressed in heart, lung, liver, kidney, small intestine, spleen, lymphe node and thymus (PubMed:25611385).
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasm
- Cytosol
- Cytoplasm
- Stress granule
- Nucleus speckle
- Chromosome
- Telomere
- Mitochondrion
- Perikaryon
- Cell projection
- Dendrite
- Cell projection
- Axon
- Predominantly localized in the nucleus. Colocalizes with SRSF2 in nuclear speckles. Colocalizes with DDX5 in nucleolar caps upon transcription inhibition. Accumulates and colocalized with TIA1 in cytoplasmic stress granules (SGs) in an arsenite-, heat shock- and RNA-binding-dependent manner. Shuttles into and out of SGs in an ATPase-dependent manner (By similarity). Colocalizes in the cytosol with the multi-helicase-TICAM1 complex that translocates to the mitochondria upon poly(I:C) stimulation (PubMed:21703541).
Alternative names
Ddx36, Kiaa1488, Mlel1, Dhx36, ATP-dependent DNA/RNA helicase DHX36, DEAD/H box polypeptide 36, DEAH box protein 36, MLE-like protein 1, RNA helicase associated with AU-rich element ARE