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| Status |
Public on Dec 04, 2022 |
| Title |
Discriminating activities of DEAD-Box Helicase 41 from myeloid malignancy-associated germline variants by genetic rescue |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although DEAD-box helicase 41 (DDX41) is implicated in oncogenic and innate immune mechanisms, there are many unanswered questions about how the ever-increasing spectrum of genetic variants impacts DDX41 activity. Here, we describe a facile genetic rescue assay that discriminates activities of DDX41 from those of human myeloid malignancy-linked germline and somatic DDX41 mutants. Our analyses revealed that the variants were impaired in their intrinsic RNA-regulatory activities and to induce monocytic differentiation markers. It will be instructive to extend these analyses to more broadly conduct structure/function assessments for clinical genetic curation and leverage the quantitative assay to elucidate mechanisms and interventions that promote and/or oppose DDX41 function, thereby influencing DDX41-linked pathogenicity.
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| Overall design |
Hoxb8-immortalized wild type hematopoietic progenitors (hi−Ddx41+/+) infected with control (empty) retrovirus, Ddx41 heterozygotic KO progenitors (hi−Ddx41+/-) infected with empty retrovirus or empty , wild type (WT) or human disease mutants of DDX41 -expressing retrovirus were FACS isolated for GFP+.
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| Contributor(s) |
Kim J, Shen S, Keles S, Bresnick EH |
| Citation(s) |
36347925 |
| |
| Submission date |
Jul 18, 2022 |
| Last update date |
Mar 05, 2023 |
| Contact name |
Siqi Shen |
| E-mail(s) |
sshen82@wisc.edu
|
| Organization name |
University of Wisconsin - Madison
|
| Street address |
425 Henry Mall
|
| City |
MADISON |
| State/province |
WI |
| ZIP/Postal code |
53705 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA859810 |
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