Alternative titles; symbols
HGNC Approved Gene Symbol: DDX17
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38) : 22:38,483,438-38,506,311 (from NCBI)
Members of the DEAD box (asp-glu-ala-asp/his) protein family of RNA helicases are involved in diverse cellular functions including mRNA splicing, ribosome assembly, translation initiation, mRNA stability, and cell growth and division (Lamm et al., 1996).
Lamm et al. (1996) cloned DDX17, which they designated p72, from a HeLa cell cDNA library. The deduced 650-amino acid protein has a calculated molecular mass of 71.9 kD. DDX17 contains 4 N-terminal RGG box repeats followed by a central conserved DEAD box domain, a run of 7 glycines, and a serine/glycine-rich C-terminal domain ending in 9 consecutive prolines. RGG box repeats mediate RNA binding, and both the serine/glycine-rich region and the proline-rich motif mediate protein-protein interactions. DDX17 shares 69.7% identity with p68 (DDX5; 180630), with highest similarity in the DEAD box region. Northern blot analysis detected ubiquitous expression of 5.3- and 9.3-kb transcripts. Both transcripts were abundantly expressed in kidney and pancreas, and the 5.3-kb transcript was also abundantly expressed in skeletal muscle. Endogenous p72 isolated from HeLa cell nuclear extracts and recombinant p72 expressed through in vitro translation yielded an apparent 79-kD protein by SDS/PAGE and Western blot analysis.
From HeLa cell cDNA, Uhlmann-Schiffler et al. (2002) cloned a variant of DDX17, which they designated p82. The deduced protein, translated from a non-AUG start codon, contains an N-terminal extension of 80 to 90 amino acids. Northern blot analysis detected this variant at about 9.3 kb in HeLa cell RNA. Both HeLa cells and COS cells endogenously expressed both DDX17 variants, which migrated at apparent molecular masses of 82 and 72 kD.
Lamm et al. (1996) confirmed that, like other DEAD box proteins, DDX17 hydrolyzed ATP in the presence of RNA. Several RNA species, including total RNA, tRNA, E. coli rRNA, and both adenovirus and beta-globin pre-mRNA, stimulated the ATPase activity. Single-stranded phage DNA also stimulated a low level of ATP hydrolysis. No activity was observed in the presence of total HeLa cell DNA or poly(U) RNA. These results led Lamm et al. (1996) to hypothesize that the ATPase activity of DDX17 is dependent on the secondary structure of RNA.
Uhlmann-Schiffler et al. (2002) determined that p82 DDX17 showed RNA-dependent ATPase activity resembling that measured in p72 DDX17. The p82 form also showed helicase activity against partial dsRNA substrates in the presence of ATP. A 3-prime single-strand overhang was required, and no helicase activity was observed with substrates containing a 5-prime single-strand overhang.
Using minigenes that undergo different types of alternative splicing, Honig et al. (2002) demonstrated that p72 DDX17 affects the splicing of alternative exons containing AC-rich exon enhancer elements. Mutation of the ATP-binding sites or deletion of the C-terminal region reduced the ability of DDX17 to effect variable exon splicing. Use of in vitro extracts overexpressing p72 DDX17 showed that p72 becomes associated with complexes containing precursor RNA. Honig et al. (2002) also found evidence that DDX17 may alter protein-RNA interactions. They concluded that DDX17 may be an alternative splicing regulatory factor.
Lee (2002) found that DDX17 catalyzed the unwinding of duplex RNA containing single-stranded regions at either the 5-prime or 3-prime end. DDX17 also copurified with U1snRNP (180740) from nuclear extracts of HeLa cell suspension cultures. This association led Lee (2002) to hypothesize that DDX17 may have a role in pre-mRNA splicing at the early stages of the splicing reaction involving U1snRNP.
By immunoprecipitation analysis, Caretti et al. (2006) found that p68, p72, and the noncoding RNA SRA (SRA1; 603819) associated with MYOD (MYOD1; 159970) in MYOD-transfected HeLa cells. In vitro and in vivo experiments identified p68, p72, and SRA as coactivators of MYOD, and their knockdown in C2C12 mouse myoblast cells prevented proper muscle gene expression and cell differentiation. Short hairpin RNA-mediated knockdown of p68 and p72 in C2C12 cells led to reduced expression of a broad spectrum of genes, including genes involved in muscle structure, metabolism, neurophysiologic processes, transcription and chromatin regulation, and signal transduction. Further experiments showed that p68 and p72 played critical roles in promoting the assembly of proteins required for formation of the transcription initiation complex and chromatin remodeling.
Stumpf (2024) mapped the DDX17 gene to chromosome 22q13.1 based on an alignment of the DDX17 sequence (GenBank AB209595) with the genomic sequence (GRCh38).
Caretti, G., Schiltz, R. L., Dilworth, F. J., Di Padova, M., Zhao, P., Ogryzko, V., Fuller-Pace, F. V., Hoffman, E. P., Tapscott, S. J., Sartorelli, V. The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev. Cell 11: 547-560, 2006. [PubMed: 17011493] [Full Text: https://doi.org/10.1016/j.devcel.2006.08.003]
Honig, A., Auboeuf, D., Parker, M. M., O'Malley, B. W., Berget, S. M. Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72. Molec. Cell. Biol. 22: 5698-5707, 2002. [PubMed: 12138182] [Full Text: https://doi.org/10.1128/MCB.22.16.5698-5707.2002]
Lamm, G. M., Nicol, S. M., Fuller-Pace, F. V., Lamond, A. I. p72: a human nuclear DEAD box protein highly related to p68. Nucleic Acids Res. 24: 3739-3747, 1996. [PubMed: 8871553] [Full Text: https://doi.org/10.1093/nar/24.19.3739]
Lee, C.-G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem. 277: 39679-39683, 2002. [PubMed: 12193588] [Full Text: https://doi.org/10.1074/jbc.C200337200]
Stumpf, A. M. Personal Communication. Baltimore, Md. 06/17/2024.
Uhlmann-Schiffler, H., Rossler, O. G., Stahl, H. The mRNA of DEAD box protein p72 is alternatively translated into an 82-kDa RNA helicase. J. Biol. Chem. 277: 1066-1075, 2002. [PubMed: 11675387] [Full Text: https://doi.org/10.1074/jbc.M107535200]