DDX17
Description
The DDX17 (DEAD-box helicase 17) is a protein-coding gene located on chromosome 22.
Probable ATP-dependent RNA helicase DDX17 (p72) is an enzyme that in humans is encoded by the DDX17 gene.
== Function == DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), 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, which is an ATPase activated by a variety of RNA species but not by dsDNA. This protein and that encoded by DDX5 gene are more closely related to each other than to any other member of the DEAD box family. Alternative splicing of this gene generates 2 transcript variants encoding different isoforms with the longer transcript reported to also initiate translation at a non-AUG (CUG) start site.
DDX17 is an RNA helicase that unwinds and alters RNA structures using ATP. It plays crucial roles in various cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing, microRNA (miRNA) processing, and transcription regulation. DDX17 regulates alternative splicing of specific exons, including promoting the inclusion of AC-rich alternative exons in CD44 transcripts. It also affects NFAT5 and histone macro-H2A.1/MACROH2A1 alternative splicing in a CDK9-dependent manner. In NFAT5, DDX17 promotes the introduction of alternative exon 4, which contains two stop codons, potentially targeting NFAT5 exon 4-containing transcripts to nonsense-mediated mRNA decay, leading to NFAT5 protein down-regulation. DDX17 also influences splicing of mediators in the steroid hormone signaling pathway, including kinases that phosphorylate ESR1, such as CDK2, MAPK1, and GSK3B, and transcriptional regulators like CREBBP, MED1, NCOR1, and NCOR2. By affecting GSK3B splicing, DDX17 contributes to ESR1 and AR stabilization. In myoblasts and epithelial cells, DDX17 collaborates with HNRNPH1 to control splicing of specific exon subsets. Beyond binding mature mRNAs, DDX17 interacts with certain pri-microRNAs, including MIR663/miR-663a, MIR99B/miR-99b, and MIR6087/miR-6087. It binds pri-microRNAs on the 3' segment flanking the stem loop via the 5'-[ACG]CAUC[ACU]-3' consensus sequence. DDX17 is essential for the production of specific microRNAs, including MIR21 and MIR125B1, and may play a role in microRNA primary transcript processing and stabilization. It participates in MYC down-regulation at high cell density by producing MYC-targeting microRNAs. Together with DDX5, DDX17 may be involved in processing the 32S intermediate into mature 28S ribosomal RNA. DDX17 is a promoter-specific transcription regulator, acting as a coactivator or corepressor depending on the promoter context and the transcriptional complex. It enhances NFAT5 transcriptional activity and synergizes with TP53 in activating the MDM2 promoter, requiring acetylation on lysine residues. DDX17 may also coactivate MDM2 transcription via a TP53-independent pathway. It coactivates MMP7 transcription and, along with CTNNB1, coactivates MYC, JUN, FOSL1, and cyclin D1/CCND1 transcription. Independently or in conjunction with DDX5 and/or SRA1 non-coding RNA, DDX17 plays a crucial role in promoting the assembly of proteins required for transcription initiation complex formation and chromatin remodeling, leading to coactivation of MYOD1-dependent transcription. This helicase-independent activity is essential for skeletal muscle cells to differentiate into myotubes. During epithelial-to-mesenchymal transition, DDX17 coregulates SMAD-dependent transcriptional activity, directly controlling key differentiation effectors, including miRNAs that in turn directly repress its expression. DDX17 participates in estrogen and testosterone signaling pathways at multiple levels, mediating the use of alternative promoters in estrogen-responsive genes and regulating the transcription and splicing of numerous steroid hormone target genes. Contrary to its splicing regulation activity, transcriptional coregulation of the estrogen receptor ESR1 is helicase-independent. DDX17 contributes to innate immunity, specifically restricting bunyavirus infection, including Rift Valley fever virus (RVFV) or La Crosse virus (LACV), but not vesicular stomatitis virus (VSV), in an interferon- and DROSHA-independent manner. It binds to RVFV RNA, likely via structured viral RNA elements. DDX17 promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1 in an ATPase-dependent manner.
DDX17 is also known as P72, RH70.
