Role of DDX41 Helicase in MDS/AML through P-bodies and Stress Granule Formation

DDX41 (DEAD-box helicase 41) is an RNA helicase required for essential aspects of RNA metabolism including ribosome biogenesis, pre-mRNA splicing, and translation. Mutations in DDX41 are linked to blood cancers, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Despite clinically reported increases in DDX41 mutations, the mechanisms resulting in MDS/AML remain unclear. Processing (P)-bodies and Stress Granules (SG) are organelles composed of RNA that play a role in regulating mRNAs under environmental stress. Wu lab has recently found that P-body formation is associated with DDX41, here we investigate the role of DDX41 in the formation of both P-bodies and stress granule formation. Using immunofluorescence and Western blot, we found that DDX41 is required for P – bodies formation but not for stress granules. This was indicated by a significant reduction in PB marker expression, whereas SG marker expression was not significantly affected. Using a GFP-tagged P-body marker (4-ET), we determined that DDX41 may play a role in mRNA splicing of P – body genes, which may be the potential mechanism behind changes in P-body dynamics. Further research is required to elucidate the precise mechanism linking mutated-DDX41, P-body dynamics, and MDS/AML.