RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II) (PubMed:25470060, PubMed:28790157). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs (PubMed:25470060). In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification. Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes (PubMed:25470060, PubMed:25477391). In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes (PubMed:25470060). Functions as cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77' (PubMed:11823437, PubMed:25260534). Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase) (PubMed:9461305). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases (PubMed:28790157). Involved in rRNA processing (PubMed:14559904, PubMed:18180292). May bind to specific miRNA hairpins (PubMed:28431233). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). ATP + H2O = ADP + H(+) + phosphate Acetylation inhibits the helicase activity. Homodimer; homodimerizes via its N-terminus. Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation. Interacts (via C-terminus) with TICAM1 (via TIR domain). Interacts with DHX36 (via C-terminus); this interaction serves as bridges to TICAM1. Interacts (via C-terminus) with DDX1 (via B30.2/SPRY domain); this interaction serves as bridges to TICAM1. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts with C1QBP. Interacts with JUN. Interacts with WDR46 (By similarity). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts with C1QBP. Interacts with JUN (PubMed:11823437, PubMed:18180292). Interacts with WDR46 (PubMed:23848194). Interacts with MCM3AP isoform GANP (PubMed:23652018). Interacts with WDR43 (By similarity). Present both in nucleolus and nucleoplasm. Interaction with JUN promotes translocation from the nucleolus to the nucleoplasm (PubMed:11823437, PubMed:18180292). Interaction with WDR46 is required for localization to the nucleolus (PubMed:23848194). Colocalizes in the cytosol with DDX1, DHX36 and TICAM1. The multi-helicase-TICAM1 complex may translocate to the mitochondria upon poly(I:C) RNA ligand stimulation (By similarity). The helicase and foldase activities reside in two separate domains, the helicase in the N-terminus and the foldase in the C-terminus. The 3 X 5 AA repeats seem to be critical for the RNA folding activity. Acetylation by CREBBP/CBP inhibits the helicase activity (PubMed:28790157). Deacetylation by SIRT7 promotes the helicase activity and overcomes R-loop-mediated stalling of RNA polymerases (PubMed:28790157). Autoantibodies against DDX21 are found in patients with watermelon stomach disease, which is characterized by prominent stripes of ectatic vascular tissue in the stomach similar to stripes on a watermelon. Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily. Extended N-terminus.