title: A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation.
abstract: G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of biological processes. To understand the biological function of G4 DNA structures and their resolvases in spermatogenesis, we investigated the distribution of G4 structures in mouse testis and identified their alterations during spermatogenesis. Meanwhile, we studied the function of RNA helicase associated with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ-cell-specific knockout mouse model. The results showed that the ablation of RHAU in germ cells caused the increase of G4 structures and thus resulted in the decrease of spermatogonial differentiation. c-kit, a spermatogonia differentiation-related gene, contains two G4 DNA motifs on its promoter. We found its expression was significantly downregulated in RHAU conditional knockout testis. A further analysis demonstrated that RHAU directly bound to the G4 structures to activate c-kit expression. We concluded that RHAU regulates spermatogonia differentiation by promoting c-kit expression via directly binding to the G4 DNA motifs c-kit promoter.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.affiliation: Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China.
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: J
authors.initials: J
authors.lastname: Nie
authors.affiliation: Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China.
authors.forename: G
authors.initials: G
authors.lastname: Yao
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230026 Anhui, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Shi
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Nanjing Biomedical Research Institute, National Resource Center for Mutant Mice, Model Animal Research Center of Nanjing University, Nanjing 210061, China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: 1] Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China [2] Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053713:Azoospermia / Q000201:enzymology / Q000473:pathology; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D045522:Recombinases / Q000378:metabolism*; D013093:Spermatogonia / Q000166:cytology* / Q000201:enzymology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000201:enzymology
chemical_list: D045522:Recombinases; D000255:Adenosine Triphosphate; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit; C466989:Dhx36 protein, mouse; D053487:DEAD-box RNA Helicases