Nucleolar RNA helicase 2
Domain
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.
Function
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 a 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).
Post-translational modifications
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).
Sequence Similarities
Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.
Cellular localization
- Nucleus
- Nucleolus
- Nucleus
- Nucleoplasm
- Cytoplasm
- Cytosol
- Mitochondrion
- 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).
Alternative names
Nucleolar RNA helicase 2, DEAD box protein 21, Gu-alpha, Nucleolar RNA helicase Gu, Nucleolar RNA helicase II, RH II/Gu, DDX21