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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''DHX36''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

Structurally, DHX36 is a 1008 amino acid-long modular

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that has been crystallized in a complex with a DNA G-quadruplex. It consists of a ~440-amino acid

helicase Helicases are a class of enzymes that are 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 double helix, separating the two hybridized ...

core comprising all signature motifs of the DEAH/RHA family of

s 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 An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of ...

called the DHX36-specific motif, which recognizes the 5'-most G-quadruplex quartet. The

OB-fold In molecular biology, the OB-fold (oligonucleotide/oligosaccharide-binding fold) is a small protein structural motif observed in different proteins that bind oligonucleotides or oligosaccharides. It was originally identified in 1993 in four unr ...

domain binds to the 3'-most G-tract sugar-phosphate backbone. 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.

Function

DEAH/RHA proteins are RNA and DNA helicases typically characterized by low

processivity In molecular biology and biochemistry, processivity is an enzyme's ability to catalyze "consecutive reactions without releasing its substrate". For example, processivity is the average number of nucleotides added by a polymerase enzyme, such as ...

translocation on substrates and the capability to bind/unwind non-canonical nucleic acid secondary structures. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation,

nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...

and

mitochondrial A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

splicing, and

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

and

spliceosome A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to sp ...

assembly. Based on their distribution patterns, some members of this DEAH/RHA

protein family A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be ...

are believed to be involved in

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...

, and cellular growth and division. DHX36 exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate ''in vitro''. 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. 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 granule In cellular biology, stress granules are biomolecular condensates in the cytosol composed of proteins and RNA that assemble into 0.1–2 μm membraneless organelles when the cell is under stress. The mRNA molecules found in stress granules a ...

s (SGs) upon translational arrest induced by various environmental stresses. A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs.

References

External links

Group Yoshikuni Nagamine homepage

EC 3.6.4 G-quadruplex {{gene-3-stub

Structure

Function

References

Further reading

External links