Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36gene.[1][2]
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.
Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrialsplicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division.[1]
RHAU exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro.[3][4] 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.[5][6] A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs.
↑Abdelhaleem M, Maltais L, Wain H (June 2003). "The human DDX and DHX gene families of putative RNA helicases". Genomics. 81 (6): 618–22. doi:10.1016/S0888-7543(03)00049-1. PMID12782131.
↑Vaughn JP, Creacy SD, Routh ED, Joyner-Butt C, Jenkins GS, Pauli S, Nagamine Y, Akman SA (November 2005). "The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates". J. Biol. Chem. 280 (46): 38117–20. doi:10.1074/jbc.C500348200. PMID16150737.
Nagase T, Kikuno R, Ishikawa K, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID10819331.
Fu JJ, Li LY, Lu GX (2002). "Molecular cloning and characterization of human DDX36 and mouse Ddx36 genes, new members of the DEAD/H box superfamily". Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao. 34 (5): 655–61. PMID12198572.
Tran H, Schilling M, Wirbelauer C, et al. (2004). "Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU". Mol. Cell. 13 (1): 101–11. doi:10.1016/S1097-2765(03)00481-7. PMID14731398.
Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID15144186.
Vaughn JP, Creacy SD, Routh ED, et al. (2006). "The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates". J. Biol. Chem. 280 (46): 38117–20. doi:10.1074/jbc.C500348200. PMID16150737.
