DHX9

Description

The DHX9 (DExH-box helicase 9) is a protein-coding gene located on chromosome 1.

ATP-dependent RNA helicase A (RHA; also known as DHX9, LKP, and NDHI) is an enzyme that in humans is encoded by the DHX9 gene.

== Function == DEAD/DEAH box helicases are proteins, and are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein with RNA helicase activity. It may participate in melting of DNA:RNA hybrids, such as those that occur during transcription, and may play a role in X-linked gene expression. It contains 2 copies of a double-stranded RNA-binding domain, a DEXH core domain and an RGG box. The RNA-binding domains and RGG box influence and regulate RNA helicase activity. The DHX9 gene is located on the long arm q of chromosome 1.

DHX9 is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction. It plays important roles in various cellular processes, including DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing. DHX9 requires a 3'-single-stranded tail as an entry site for unwinding nucleic acids and can bind and hydrolyze any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs). It can unwind various nucleic acid substrates, including double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks, D- and R-loops, triplex-helical DNA (H-DNA), and G-quadruplexes. DHX9 binds to dsDNA, ssDNA, dsRNA, ssRNA, and poly(A)-containing RNA. It also binds to circular dsDNA or dsRNA, stimulating the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A. DHX9 contributes to DNA replication at origins of replication and cell cycle progression. It acts as a transcriptional coactivator, bridging the polymerase II holoenzyme with transcription factors or cofactors, such as BRCA1, CREBBP, RELA, and SMN1. It binds to the CDKN2A promoter and plays roles in post-transcriptional regulation of gene expression. In cooperation with NUP98, it promotes pre-mRNA alternative splicing of a subset of genes. As a component of the large PER complex, it participates in the negative regulation of 3' transcriptional termination of circadian target genes, such as PER1 and NR1D1, and the control of circadian rhythms. DHX9 acts as a nuclear resolvase, binding and neutralizing harmful double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements. It positively regulates nuclear export of unspliced mRNA containing the constitutive transport element (CTE). DHX9 is a component of the coding region determinant (CRD)-mediated complex, promoting cytoplasmic MYC mRNA stability. It plays a role in mRNA translation, positively regulating translation of selected mRNAs through its binding to the post-transcriptional control element (PCE) in the 5'-UTR. DHX9 is involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding to a specific stem-loop structure in their 5'-UTRs. It stimulates LIN28A-dependent mRNA translation by facilitating ribonucleoprotein remodeling. DHX9 functions as a small interfering (siRNA)-loading factor involved in RNA-induced silencing complex (RISC) loading complex (RLC) assembly, participating in RISC-mediated gene silencing. It binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection. This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory responses, including IL18 release and pyroptosis. Finally, DHX9 mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus.

DHX9 is also known as DDX9, LKP, NDH2, NDHII, RHA.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing