DHX9 Protein, Human (His)

DHX9 is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction, playing critical roles in processes such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing. It requires a 3'-single-stranded tail for unwinding activity and can bind and hydrolyze any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs). DHX9 unwinds diverse substrates, including double-stranded (ds) DNA/RNA, DNA:RNA hybrids, forks, displacement loops (D-loops/R-loops), triplex-helical DNA (H-DNA), and G-quadruplexes. It binds various nucleic acids (dsDNA, ssDNA, dsRNA, ssRNA, poly(A)-RNA) and stimulates TOP2A-mediated relaxation of supercoiled DNA. DHX9 functions in DNA replication at origins and cell cycle progression, acting as a transcriptional coactivator bridging RNA polymerase II with factors like BRCA1, CREBBP, RELA, and SMN1. It regulates post-transcriptional gene expression, cooperates with NUP98 to promote alternative splicing, and, as part of a PER complex, negatively regulates circadian gene termination (e.g., PER1, NR1D1) (by similar). It also resolves harmful dsRNA structures from Alu retrotransposons. DHX9 enhances nuclear export of constitutive transport element (CTE)-containing mRNAs, stabilizes MYC mRNA via the coding region determinant (CRD) complex, and promotes translation by binding 5'-UTR elements (PCE) or collaborating with LARP6 for collagen mRNA translation. It facilitates LIN28A-dependent translation and participates in RISC assembly for siRNA-mediated silencing. DHX9 binds rotavirus-derived dsRNA, potentially activating NLRP9 inflammasome and triggering IL18 release and pyroptosis. Lastly, it mediates hnRNP attachment to nuclear actin filaments.