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DDX41 is a DEAD-box helicase and is conserved across species. Mutations in DDX41 have been associated with myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia. Though its pathogenesis is not completely known, DDX41 has been shown to have many cellular roles, including in pre-mRNA splicing, innate immune sensing, ribosome biogenesis, translational regulation, and R-loop metabolism. In this review, we will summarize the latest understandings regarding the various roles of DDX41, as well as highlight challenges associated with drug development to target DDX41. Overall, understanding the molecular and cellular mechanisms of DDX41 could help develop novel therapeutic options for DDX41 mutation-related hematologic malignancies.
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http://dx.doi.org/10.1042/BST20230725 | DOI Listing |
EMBO Rep
August 2025
Institute of Epigenetics and Stem Cells (IES), Helmholtz Munich, Feodor-Lynen-Strasse 21, Munich, 81377, Germany.
The CGG triplet repeat binding protein 1 (CGGBP1) binds to CGG repeats and has several important cellular functions, but how this DNA sequence-specific binding factor affects transcription and replication processes is an open question. Here, we show that CGGBP1 binds human gene promoters containing short (< 5) CGG-repeat tracts prone to R-loop formation. Loss of CGGBP1 leads to deregulated transcription, transcription-replication-conflicts (TRCs) and accumulation of Serine-5 phosphorylated RNA polymerase II (RNAPII), indicative of promoter-proximal stalling and a defect in transcription elongation.
View Article and Find Full Text PDFBlood Cancer J
August 2025
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Management paradigms for newly-diagnosed acute myeloid leukemia (ND-AML) in patients considered unfit to receive intensive chemotherapy have evolved with improved understanding of disease biology. In this setting, management requires clear delineation of goals of therapy that should include preservation of quality-of-life (QoL). Combination of venetoclax (Ven) and a hypomethylating agent (HMA) is the current standard-of-care in most circumstances with flexible options in regard to drug dose and duration of treatment as well as the addition (triplet combinations) or alternative use of targeted therapies, such as inhibitors of FLT3, IDH1, IDH2, or menin for patients with NPM1 or KMT2A rearrangements (KMT2Ar).
View Article and Find Full Text PDFFront Immunol
August 2025
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
The 2002 movie is a cat-and-mouse story in which Frank Abagnale Jr. successfully conned his way into several high-profile jobs while evading capture by FBI agent Carl Hanratty. Similarly, after entering host cells, viruses interact with or hijack host cellular machinery to replicate their genetical materials and assemble themselves for the next round of infection.
View Article and Find Full Text PDFNat Commun
August 2025
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
The RNA helicase DDX41 is a DEAD-box helicase that is well known as a virus sensor in dendritic cells and a tumor suppressor that is frequently mutated in myeloid neoplasms. However, the functions and relevance of DDX41 in solid tumors remain largely unexplored. In this study, through in vivo CRISPR screening, we demonstrate that DDX41 is highly expressed in various solid tumor types and promotes tumorigenicity in liver cancer.
View Article and Find Full Text PDFbioRxiv
July 2025
Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Accurate splicing, which involves the controlled removal of non-coding sequences (introns) from precursor messenger RNAs (pre-mRNAs), is essential for producing correct mature mRNAs that encode functional proteins. Within pre-mRNAs, latent splice sites (LSSs) resemble proper splice sites but are usually not used because their activation can introduce in-frame STOP codons. The nuclear suppression of splicing (SOS) mechanism prevents the use of LSSs.
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