RHAU (RNA Helicase associated with AU-rich element, also known as DHX36 or G4R1) is a 114-kDa human RNA helicase of the DEAH-box family of helicases encoded by the DHX36 gene. [1]
Structurally, RHAU is a 1008 amino acid-long modular protein. It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH-box family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Like all the DEAH-box proteins, the helicase associated domain is located adjacent to the helicase core region and occupies 75% of the C-terminal region.
RHAU exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro. [2] [3] RHAU 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, RHAU was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.
Previous work showed that RHAU associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses. [4] [5] A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs. [4]
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.
In cellular biology, stress granules are biomolecular condensates in the cytosol composed of proteins and RNAs that assemble into 0.1–2 μm membraneless organelles when the cell is under stress. The mRNA molecules found in stress granules are stalled translation pre-initiation complexes associated with 40S ribosomal subunits, translation initiation factors, poly(A)+ mRNAs and RNA-binding proteins (RBPs). While they are membraneless organelles, stress granules have been proposed to be associated with the endoplasmatic reticulum. There are also nuclear stress granules. This article is about the cytosolic variety.
In biochemistry, two biopolymers are antiparallel if they run parallel to each other but with opposite directionality (alignments). An example is the two complementary strands of a DNA double helix, which run in opposite directions alongside each other.
Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the HSF1 gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.
Nucleolin is a protein that in humans is encoded by the NCL gene.
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 DDX17 (p72) is an enzyme that in humans is encoded by the DDX17 gene.
TAR DNA-binding protein 43 is a protein that in humans is encoded by the TARDBP gene.
DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.
Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene.
Glutaminyl-tRNA synthetase is an enzyme that in humans is encoded by the QARS gene.
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.
The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA.
GCN2 is a serine/threonine-protein kinase that senses amino acid deficiency through binding to uncharged transfer RNA (tRNA). It plays a key role in modulating amino acid metabolism as a response to nutrient deprivation.
SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene.
RRM3 is a gene that encodes a 5′-to-3′ DNA helicase known affect multiple cellular replication and repair processes and is most commonly studied in Saccharomyces cerevisiae. RRM3 formally stands for Ribosomal DNArecombination mutation 3. The gene codes for nuclear protein Rrm3p, which is 723 amino acids in length, and is part of a Pif1p DNA helicase sub-family that is conserved from yeasts to humans. RRM3 and its encoded protein have been shown to be vital for cellular replication, specifically associating with replication forks genome-wide. RRM3 is located on chromosome 8 in yeast cells and codes for 723 amino acids producing a protein that weighs 81,581 Da.
PIF1 5'-to-3' DNA helicase is a protein that in humans is encoded by the PIF1 gene.
