The DEAD box RNA helicase DDX3X is required in natural killer cells

Abstract The X-chromosome linked RNA helicase DDX3X plays multiple roles in metabolism and antiviral interferon responses. Some viruses, including SARS-CoV-2, usurp the function of to support viral genome replication evasion interferon. These findings have led development inhibitors as potential agents. However, somatic loss mutations this are neurological disease malignancies, a form non-Hodgkin’s lymphoma initiated natural killer (NK) cell lineage. Given critical role NK cells antitumor immunity, we sought determine how inhibition could affect NK-cell biology. Constitutive (Ncr1-iCre) or inducible (Ncr1-iCreER T2) deletion Ddx3x Ncr1-expressing (i.e. cells) mice resulted complete peripheral cells. Addition inhibitor RK-33 vitro cultures similar cellularity, while blocked from progenitor an culture on stromal Preliminary analyses suggest that results rapid death committed Partial preservation early stages bone marrow male but not female Ncr1 DDdx3xsuggests Y-chromosome DDX3Y may compensate for supporting survival at earliest differentiation. We identify crucial DDX3 helicases implications clinical use R01 AI148080 AR073228