Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase 1 (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36 gene. [5] [6]
Structurally, DHX36 is a 1008 amino acid-long modular protein that has been crystallized in a complex with a DNA G-quadruplex. [7] It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH/RHA family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Part of the N-terminal flanking region forms an alpha-helix called the DHX36-specific motif, which recognizes the 5'-most G-quadruplex quartet. The OB-fold domain binds to the 3'-most G-tract sugar-phosphate backbone. [8] Like all the DEAH/RHA helicases, the helicase associated domain is located adjacent to the helicase core region and occupies 75% of the C-terminal region. [9]
DEAH/RHA proteins are RNA and DNA helicases typically characterized by low processivity translocation on substrates and the capability to bind/unwind non-canonical nucleic acid secondary structures. [10] They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAH/RHA protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. [5]
DHX36 exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro. [11] [12] DHX36 displays repetitive unwinding activity as a function of the thermal stability of the G-quadruplex substrate, characteristic of a number of other G-quadruplex resolvases such as the BLM/WRN helicases. [13] [14] DHX36 binds G4-nucleic acid with sub-nanomolar affinity and unwinds G4 structures much more efficiently than double-stranded nucleic acid. Consistent with these biochemical observations, DHX36 was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.
Previous work showed that DHX36 associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses. [15] [16] A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs.
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have to be associated with a sequence motif; it can be represented by different and completely unrelated sequences in different proteins or RNA.
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two hybridized nucleic acid strands, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases.
In molecular biology, G-quadruplex secondary structures (G4) are formed in nucleic acids by sequences that are rich in guanine. They are helical in shape and contain guanine tetrads that can form from one, two or four strands. The unimolecular forms often occur naturally near the ends of the chromosomes, better known as the telomeric regions, and in transcriptional regulatory regions of multiple genes, both in microbes and across vertebrates including oncogenes in humans. Four guanine bases can associate through Hoogsteen hydrogen bonding to form a square planar structure called a guanine tetrad, and two or more guanine tetrads can stack on top of each other to form a G-quadruplex.
DEAD box proteins are involved in an assortment of metabolic processes that typically involve RNAs, but in some cases also other nucleic acids. They are highly conserved in nine motifs and can be found in most prokaryotes and eukaryotes, but not all. Many organisms, including humans, contain DEAD-box (SF2) helicases, which are involved in RNA metabolism.
ATP-dependent RNA helicase A is an enzyme that in humans is encoded by the DHX9 gene.
Probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 is an enzyme that in humans is encoded by the DDX5 gene.
Probable ATP-dependent RNA helicase DDX17 (p72) is an enzyme that in humans is encoded by the DDX17 gene.
Eukaryotic initiation factor 4A-I is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. eIF4A1 unwinds the secondary structure of RNA within the 5'-UTR of mRNA, a critical step necessary for the recruitment of the 43S preinitiation complex, and thus the translation of protein in eukaryotes. It was first characterized in 1982 by Grifo, et al., who purified it from rabbit reticulocyte lysate.
Probable ATP-dependent RNA helicase DDX6 is an enzyme that in humans is encoded by the DDX6 gene.
Probable ATP-dependent RNA helicase DDX11 is an enzyme that in humans is encoded by the DDX11 gene.
Nucleolar RNA helicase 2 is an enzyme that in humans is encoded by the DDX21 gene.
Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 is an enzyme that in humans is encoded by the DHX38 gene.
ATP-dependent RNA helicase DDX39 is an enzyme that in humans is encoded by the DDX39 gene.
Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX15 is an enzyme that in humans is encoded by the DHX15 gene.
Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 is an enzyme that in humans is encoded by the DHX32 gene.
Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 is an enzyme that in humans is encoded by the DHX16 gene.
RHAU is a 114-kDa human RNA helicase of the DEAH-box family of helicases encoded by the DHX36 gene.
DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene.
PIF1 5'-to-3' DNA helicase is a protein that in humans is encoded by the PIF1 gene.
DEAH-box helicase 8, is a protein that in humans is encoded by the DHX8 gene. This protein is member of the DEAH box polypeptide family. The main characteristic of this group is their conserved motif DEAH. A wide range of RNA helicases belongs to this family. Specifically, DHX8 acts as an ATP-dependent RNA helicase involved in splicing and the regulation of the releasing of spliced mRNAs from spliceosomes out of the nucleus. Published studies have shown the consequences of DHX8 mutations, some of them are critical for biological processes such as hematopoiesis and are related to some diseases.
 | This article on a gene on human chromosome 3 is a stub. You can help Wikipedia by expanding it. |
