Ddx42, a DEAD box RNA helicase, is involved in multiple biological processes. It plays a role in nucleic acid metabolism, as DExH/D-box helicases are essential for aspects like replication, gene expression, and post-transcriptional modifications [3]. It is also associated with the assembly of human U2 snRNP [2].

Genome-wide screens have identified Ddx42 as an intrinsic antiviral inhibitor. Depletion of endogenous Ddx42 increases HIV-1 DNA accumulation and infection in cell lines and primary cells, while its overexpression inhibits HIV-1 infection. Ddx42 also restricts LINE-1 retrotransposition and infection with other retroviruses and positive-strand RNA viruses, such as CHIKV and SARS-CoV-2, but does not impact the replication of several negative-strand RNA viruses [1]. In addition, Ddx42 interacts with paxillin in Ba/F3 cells, regulating apoptosis and polarization [4]. In cholangiocarcinoma, circ_0007534, derived from the Ddx42 gene, can form a complex with DDX3X to enhance Ddx42 mRNA stability, promoting cancer progression [5].

In conclusion, Ddx42 has diverse functions, acting as an intrinsic inhibitor of positive-strand RNA viruses, participating in U2 snRNP assembly, and influencing cell survival and polarization. Its role in viral infections and cancer progression, as revealed through functional studies, provides insights into potential therapeutic targets for related diseases.