RESUMO
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.
Assuntos
RNA Helicases DEAD-box/fisiologia , Hematopoese/genética , Regiões Promotoras Genéticas/genética , Anemia Hemolítica Congênita/genética , Animais , Transplante de Medula Óssea , Ciclo Celular , Cruzamentos Genéticos , RNA Helicases DEAD-box/deficiência , RNA Helicases DEAD-box/genética , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/fisiologia , Eritroblastos/patologia , Eritropoetina/sangue , Genes Letais , Genes Sintéticos , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Hematopoese/fisiologia , Leucopenia/congênito , Leucopenia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dobramento de Proteína , Proteínas Proto-Oncogênicas c-vav/genética , Quimera por Radiação , Recombinases/deficiência , Recombinases/genética , Recombinases/fisiologia , Trombocitopenia/congênito , Trombocitopenia/genéticaRESUMO
Considering the high and increasing prevalence of stress, approaches to mitigate stress-related biological processes become a matter of public health. Since supportive social interactions contribute substantially to mental and physical health, we set out to develop a social support stress management intervention and examined its effects on psychophysiological stress responses as well as self-reported stress in healthy women. In a parallel-group randomized controlled trial, registered in the DSRK (DRKS00017427), 53 healthy women were randomly assigned to a social support stress management or a waitlist control condition. All participants underwent a standardized psychosocial stress test where physiological and emotional stress responses were assessed by repeated measurements of cortisol, heart rate, heart rate variability and state anxiety. Also, all participants completed self-report questionnaires of perceived stress and social support at pre-intervention, post-intervention and follow-up four weeks later. Participants in the social support stress management showed a significantly attenuated integrated state anxiety response in comparison to those in the control condition, but conditions did not differ in any of the assessed physiological stress responses. The intervention significantly reduced perceived stress in comparison to the control condition, but perceived stress levels returned to baseline at follow-up. Our results indicated that the intervention had no effect on physiological responses to acute psychosocial stress, even though anxiety responses to stress were attenuated. However, the social support stress management intervention had a significant, albeit transient impact on perceived stress.