Dhx16-KO Mouse

Dhx16, also known as DBP2 (DEAD-box protein 2), is an ATP-dependent RNA helicase and a key spliceosome component. It plays a vital role in processes like pre-mRNA splicing, ribosome assembly, and innate antiviral immunity [1,2,3,4,5]. In pre-mRNA splicing, it functions after the formation of a pre-catalytic spliceosome, similar to the role of Saccharomyces cerevisiae spliceosomal ATPase Prp2 [3].

Using conditional knockout (CKO) mice, it was demonstrated that loss of Dhx16 in the hematopoietic system leads to significant depletion of hematopoietic stem and progenitor cells, bone marrow failure, and rapid mortality. Dhx16-deficient HSCs show impaired quiescence, cell cycle arrest, reduced protein synthesis, abnormal ribosome assembly, increased apoptosis, and decreased self-renewal capacity [2]. In addition, silencing of Dhx16 in cells and in vivo diminished type I interferon (IFN-I) responses against influenza virus, Zika virus, and SARS-CoV-2. Dhx16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6 [1].

In conclusion, Dhx16 is crucial for processes such as pre-mRNA splicing, ribosome assembly, and innate antiviral immunity. Studies using CKO mouse models have revealed its significance in maintaining hematopoietic stem cell homeostasis and in antiviral defense. These findings contribute to our understanding of hematopoietic diseases and antiviral immunity, potentially providing insights for therapeutic strategies.