RNA helicase A interacts with dsDNA and topoisomerase IIalpha

Zhou, Kai; Choe, Kyoo Tae; Zaidi, Zaheer; Wang, Qi; Mathews, Michael B.; Lee, Chee Gun

doi:10.1093/nar/gkg328

Cited by 45 publications

(49 citation statements)

References 51 publications

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“…These proteins are highly conserved from viruses and bacteria to humans (26). Although initially classified as RNA helicases, many members of the DExD/H helicase family, including DHX36 and DHX9, were found to display DNA helicase activity (27,28). Sequence analyses revealed that DHX36 and DHX9 are in the same DEAH/RHA helicase subfamily, which is close to but is clearly separated from the RIG-I-like helicase subfamily (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Kim

Pazhoor

Bao

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

285

302

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Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the presence of myeloid differentiation primary response gene 88 (MyD88)-dependent DNA sensors other than TLR9 in pDCs. Using MS, we investigated C-phosphate-G (CpG)-binding proteins from human pDCs, pDC-cell lines, and interferon regulatory factor 7 (IRF7)-expressing B-cell lines. CpG-A selectively bound the aspartate-glutamate-any amino acid-aspartate/histidine (DExD/H)-box helicase 36 (DHX36), whereas CpG-B selectively bound DExD/H-box helicase 9 (DHX9). Although the aspartateglutamate-alanine-histidine box motif (DEAH) domain of DHX36 was essential for CpG-A binding, the domain of unknown function 1605 (DUF1605 domain) of DHX9 was required for CpG-B binding. DHX36 is associated with IFN-α production and IRF7 nuclear translocation in response to CpG-A, but DHX9 is important for TNF-α and IL-6 production and NF-κB activation in response to CpG-B. Knocking down DHX9 or DHX36 significantly reduced the cytokine responses of pDCs to a DNA virus but had no effect on the cytokine responses to an RNA virus. We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.cytosolic sensor | innate immunity

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Section: Resultsmentioning

confidence: 99%

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Kim

Pazhoor

Bao

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

285

302

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“…RHA, also known as DHX9, is a 130-kDa protein which belongs to the DEXD/H box family of proteins. Members of this family act as ATP-driven motors and can unwind both double-stranded RNA and DNA (50,51) or control switches at very specific points in processes such as pre-mRNA splicing or during ribosome biogenesis (17). In addition to its helicase activity, with the energy derived from ATP, RHA is able to bind and remodel RNA or RNA-protein complexes and subsequently regulates many aspects of cellular RNA metabolism, such as transcription, RNA nuclear export, and translation initiation (9,17).…”

Section: Discussionmentioning

confidence: 99%

Identification of RNA Helicase A as a Cellular Factor That Interacts with Influenza A Virus NS1 Protein and Its Role in the Virus Life Cycle

Lin

Pyo

et al. 2012

J Virol

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“…In addition to a core helicase domain, there are also extending N-terminal and Cterminal domains that are thought to be involved in proteinprotein/RNA interactions (20). Although generally believed to contain probable RNA helicase/unwindase activity, some members of the DDX/DHX family, such as DHX9 (also called RNA helicase A), have also been shown to bind DNA and function as a DNA helicase (53). In fact, DEAH RNA helicases contain some degree of structural homology to DNA helicases (13).…”

Section: Discussionmentioning

confidence: 99%

Identification of DHX33 as a Mediator of rRNA Synthesis and Cell Growth

Zhang

Forys

Miceli

et al. 2011

Molecular and Cellular Biology

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In this report, we employed a lentiviral RNA interference screen to discover nucleolar DEAD/DEAH-box helicases involved in RNA polymerase I (Pol I)-mediated transcriptional activity. Our screen identified DHX33 as an important modulator of 47S rRNA transcription. We show that DHX33 is a cell cycle-regulated nucleolar protein that associates with ribosomal DNA (rDNA) loci, where it interacts with the RNA Pol I transcription factor upstream binding factor (UBF). DHX33 knockdown decreased the association of Pol I with rDNA and caused a dramatic decrease in levels of rRNA synthesis. Wild-type DHX33 overexpression, but not a DNA binding-defective mutant, enhanced 47S rRNA synthesis by promoting the association of RNA polymerase I with rDNA loci. In addition, an NTPase-defective DHX33 mutant (K94R) acted as a dominant negative mutant, inhibiting endogenous rRNA synthesis. Moreover, DHX33 deficiency in primary human fibroblasts triggered a nucleolar p53 stress response, resulting in an attenuation of proliferation. Thus, we show the mechanistic importance of DHX33 in rRNA transcription and proliferation.RNA is a highly structured macromolecule whose secondary and tertiary conformations facilitate an array of specific interactions with proteins. The DEAD/DEAH-box family of RNA helicases (here referred to as DDX/DHX) (3) is one such classification of RNA binding proteins that are capable of modifying the higher-ordered structures of RNA through the hydrolysis of ATP/nucleoside triphosphate (NTP) (41). DDX/ DHX proteins often form large multiprotein complexes that participate in fundamental biological activities such as RNA transcription, RNA editing, pre-mRNA splicing, ribosome biogenesis, and RNA decay (3).DDX/DHX helicases are named and characterized by the conserved DEAD/DEAH motif common among all family members. Through site-directed mutagenesis analysis, DEAD/ DEAH along with seven conserved peptide motifs have been found to participate in ATP/NTP binding, hydrolysis, and substrate binding (28). Despite the conservation of these peptide motifs, the remaining sequences within each RNA helicase family member vary widely. Specifically, differences exist between the two categories of DDX and DHX proteins. DDX proteins contain a unique Q motif at their N termini that distinguishes them from DHX proteins. It was proposed previously that the Q motif might sense the state of ATP in vivo (40), given that DHX-box proteins are promiscuous in their ability to utilize NTP (16).Ribosome biogenesis is a complex multistep process, the majority of which occurs in the nucleolus of the cell (24, 43). The transcription of ribosomal DNA (rDNA) is the initial and rate-limiting step in ribosome biogenesis, and as such, it is influenced by multiple levels of regulation (25). One of the key regulators of rDNA transcription is the upstream binding factor (UBF), a transcriptional transactivator that binds to the upstream core element of rDNA and subsequently bends rDNA (37). This change in the rDNA structure favors the binding of SL.1 as wel...

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RNA helicase A interacts with dsDNA and topoisomerase IIalpha

Cited by 45 publications

References 51 publications

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Identification of RNA Helicase A as a Cellular Factor That Interacts with Influenza A Virus NS1 Protein and Its Role in the Virus Life Cycle

Identification of DHX33 as a Mediator of rRNA Synthesis and Cell Growth

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