Lai, Ching Janice. The DEAH helicase RHAU is essential for embryogenesis and hematopoiesis. 2012, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9914
Conventional RHAU ablation caused embryonic lethality before 7.5 days after fertilization but without disturbing embryo implantation, suggesting a fundamental role for RHAU in early development (gastrulation).
Because conventional RHAU-ablation caused embryonic lethality, we then targeted the RHAU gene specifically in the hematopoiesis system. To achieve this we used vav1-iCre system, in which iCre gene (an optimized variant of Cre recombinase) was expressed under the control of vav1 oncogen promoter that was active solely in the hematopoietic system. Results showed that RHAU-ablation in the hematopoietic system strongly affected the process of hematopoiesis in a lineage- and stage-specific manner. Notably, RHAU ablation caused hemolytic anemia and strong impairment of lymphoid cell differentiation at early its stages.
Finally, by micro-array analysis we examined the effect of RHAU ablation on the change of transcriptome in proerythroblasts. We found that within a group of genes involved in cell death and cell cycle regulation, RHAU-ablation deregulated those genes that contained G-quadruplex motifs in their promoter regions. This result suggests that RHAU plays a role in the regulation of gene expression through involving its G4 resolvase activity.
|Advisors:||Skoda, Radek C.|
|Committee Members:||Matthias, Patrick D. and Hynes, Nancy|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Hematology (Skoda)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||108 S.|
|Last Modified:||30 Jun 2016 10:49|
|Deposited On:||04 Jul 2012 14:46|
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