title: The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis.
abstract: The DEAH helicase RHAU (alias DHX36, G4R1) is the only helicase shown to have G-quadruplex (G4)-RNA resolvase activity and the major source of G4-DNA resolvase activity. Previous report showed RHAU mRNA expression to be elevated in human lymphoid and CD34(+) BM cells, suggesting a potential role in hematopoiesis. Here, we generated a conditional knockout of the RHAU gene in mice. Germ line deletion of RHAU led to embryonic lethality. We then targeted the RHAU gene specifically in the hematopoiesis system, using a Cre-inducible system in which an optimized variant of Cre recombinase was expressed under the control of the Vav1 promoter. RHAU deletion in hematopoietic system caused hemolytic anemia and differentiation defect at the proerythroblast stage. The partial differentiation block of proerythroblasts was because of a proliferation defect. Transcriptome analysis of RHAU knockout proerythroblasts showed that a statistically significant portion of the deregulated genes contain G4 motifs in their promoters. This suggests that RHAU may play a role in the regulation of gene expression that relies on its G4 resolvase activity.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66,Basel, Switzerland.
authors.forename: Janice Ching
authors.initials: JC
authors.lastname: Lai
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ponti
authors.forename: Dejing
authors.initials: D
authors.lastname: Pan
authors.forename: Hubertus
authors.initials: H
authors.lastname: Kohler
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Nagamine
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D003433:Crosses, Genetic; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D004900:Erythroblasts / Q000473:pathology; D004921:Erythropoietin / Q000097:blood; D005804:Genes, Lethal; D005813:Genes, Synthetic; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D007970:Leukopenia / Q000151:congenital / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017510:Protein Folding; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics; D011828:Radiation Chimera; D045522:Recombinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013921:Thrombocytopenia / Q000151:congenital / Q000235:genetics
chemical_list: D051567:Proto-Oncogene Proteins c-vav; D045522:Recombinases; C496619:Vav1 protein, mouse; D004921:Erythropoietin; D049452:Green Fluorescent Proteins; C466989:Dhx36 protein, mouse; D053487:DEAD-box RNA Helicases