Untitled

Krishnan, Vyjayanthi; Zeichner, Steven L.

doi:10.1186/1742-4690-1-42

Cited by 49 publications

(27 citation statements)

References 36 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yeast Ded1 was shown to function in the 5’ noncoding region of BMV RNA2 , which encodes viral polymerase-like protein 2a, through a translational mechanism [30]. In addition to DDX3, other DEAD-box proteins also exhibit different expression patterns during HIV-1 replication [41]. For example, DDX1 was identified as a cellular cofactor for the Rev/RRE/CRM1-mediated export of HIV-1 mRNAs [42].…”

Section: Discussionmentioning

confidence: 99%

Human DDX3 Interacts with the HIV-1 Tat Protein to Facilitate Viral mRNA Translation

et al. 2013

View full text Add to dashboard Cite

Nuclear export and translation of intron-containing viral mRNAs are required for HIV-1 gene expression and replication. In this report, we provide evidence to show that DDX3 regulates the translation of HIV-1 mRNAs. We found that knockdown of DDX3 expression effectively inhibited HIV-1 production. Translation of HIV-1 early regulatory proteins, Tat and rev, was impaired in DDX3-depleted cells. All HIV-1 transcripts share a highly structured 5’ untranslated region (UTR) with inhibitory elements on translation of viral mRNAs, yet DDX3 promoted translation of reporter mRNAs containing the HIV-1 5’ UTR, especially with the transactivation response (TAR) hairpin. Interestingly, DDX3 directly interacts with HIV-1 Tat, a well-characterized transcriptional activator bound to the TAR hairpin. HIV-1 Tat is partially targeted to cytoplasmic stress granules upon DDX3 overexpression or cell stress conditions, suggesting a potential role of Tat/DDX3 complex in translation. We further demonstrated that HIV-1 Tat remains associated with translating mRNAs and facilitates translation of mRNAs containing the HIV-1 5’ UTR. Taken together, these findings indicate that DDX3 is recruited to the TAR hairpin by interaction with viral Tat to facilitate HIV-1 mRNA translation.

show abstract

Section: Discussionmentioning

confidence: 99%

Human DDX3 Interacts with the HIV-1 Tat Protein to Facilitate Viral mRNA Translation

et al. 2013

View full text Add to dashboard Cite

show abstract

“…When the RNA helicase named RH116 was overexpressed, levels of full-length and single spliced HIV-1 RNA transcripts were increased through an undefined mechanism (40). The expression levels of a number of DEAD-box proteins, such as DDX10, DDX18, DDX21, DDX23, DDX39, and DDX52, in HIV-1 latently infected ACH-2 cells changed upon treatment with phorbol 12-myristate 13-acetate (41). However, the functions of these latter DEAD-box proteins in HIV-1 replication have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Association of RNA Helicase A with Human Immunodeficiency Virus Type 1 Particles

Roy

Guo

et al. 2006

Journal of Biological Chemistry

132

View full text Add to dashboard Cite

RNA helicase A (RHA) belongs to the DEAH family of proteins that are capable of unwinding double-stranded RNA structure. In addition to its involvement in the metabolism of cellular RNA, RHA has been shown to stimulate RNA transcription from the long terminal repeat promoter of human immunodeficiency virus type 1 (HIV-1) as well as to enhance Rev/Rev response element-mediated gene expression. In this study, we provide evidence that RHA associates with HIV-1 Gag in an RNA-dependent manner. This interaction results in specific incorporation of RHA into HIV-1 particles. Knockdown of endogenous RHA in virus producer cells leads to generation of HIV-1 particles that are less infectious in part as a result of restricted reverse transcription. Therefore, RHA represents the first example of cellular RNA helicases that participate in HIV-1 particle production and promote viral reverse transcription. RNA helicase A (RHA)2 is a member of the DEXH-box (where X can be any amino acid) family of proteins and is also termed DHX9 (1, 2). The DEXH-box proteins, together with the DEAD-box and the Ski2 family members, are referred to as RNA helicases that are able to rearrange the structures of RNA molecules (3). RHA contains a helicase core domain consisting of seven motifs that are conserved for all RNA helicases. Within the N-terminal region of RHA there are two copies of type A double-stranded RNA binding domains. Together with an RGG-box domain located at the C terminus, double-stranded RNA binding domains regulate RNA binding as well as helicase activities of RHA (4). RHA is a nuclear protein and shuttles between the nucleus and the cytoplasm with the assistance of a bidirectional nuclear transport domain consisting of 110 amino acids at the C terminus (5). This function of the RHA nuclear transport domain is subject to regulation of arginine methylation catalyzed by PRMT1 (protein-arginine methyltransferase 1) (6). RHA is able to unwind double-stranded RNA or DNA with the energy derived from hydrolysis of NTPs by virtue of its NTPase activity (1). This property enables RHA to participate in multiple cellular processes from RNA transcription to RNA processing to RNA nuclear export (7). These multiple functions underlie the vital role of RHA in the germ line proliferation and development of Caenorhabditis elegans (8) and also account for the early embryonic lethality observed with RHA knock-out mice (9).The regulation activity of RHA in RNA transcription is implicated by its presence within the RNA polymerase II holoenzyme complex. For example, RHA has been shown to bridge the interactions between RNA polymerase II and transcription co-activators such as CREB-binding protein and BRAC1 (breast cancer-specific tumor suppressor protein 1) (10, 11). RHA also directly interacts with the p65 subunit of NF-B and stimulates NF-B-mediated reporter gene expression (12). Involvement of RHA in transcription is further indicated by the function of its homologue in Drosophila, named the maleless (MLE) gene, that increases gene expression fr...

show abstract

“…DDX3X is one of several DEAD box protein genes that are upregulated during HIV-1 replication [64]. Then, REV, an HIV encoded protein, interacts directly with the CRM1 protein and utilizes this pathway to export unspliced and partially spliced HIV-1 transcripts (which normally are not exported) from the nucleus to the cytoplasm [58].…”

Section: Distribution and Function Of Ddx3 Subfamily Members In Humanmentioning

confidence: 99%

The DDX3 Subfamily of the DEAD Box Helicases: Divergent Roles as Unveiled by Studying Different Organisms and In Vitro Assays

Rosner

Rinkevich

2007

CMC

View full text Add to dashboard Cite

DDX3 (or Ded1p), the highly conserved subfamily of the DEAD-box RNA helicase family (40 members in humans), plays important roles in RNA metabolism. DDX3X and DDX3Y, the two human paralogous genes of this subfamily of proteins, have orthologous candidates in a diverse range of eukaryotes, from yeast and plants to animals. While DDX3Y, which is essential for normal spermatogenesis, is translated only in the testes, DDX3X protein is ubiquitously expressed, involved in RNA transcription, RNA splicing, mRNA transport, translation initiation and cell cycle regulation. Studies of recent years have revealed that DDX3X participates in HIV and hepatitis C viral infections, and in hepatocellular carcinoma, a complication of hepatitis B and hepatitis C infections. In the urochordates (i.e., Botryllus schlosseri) and in diverse invertebrate phyla (represented by model organisms such as: Drosophila, Hydra, Planaria), DDX3 proteins (termed also PL10) are involved in developmental pathways, highly expressed in adult undifferentiated soma and germ cells and in some adult and embryo's differentiating tissues. As the mechanistic and functional knowledge of DDX3 proteins is limited, we suggest assembling the available data on DDX3 proteins, from all studied organisms and in vitro assays, depicting a unified mechanistic scheme for DDX3 proteins' functions. Understanding the diverse functions of DDX3 in multicellular organisms may be particularly important for effective strategies of drug design.

show abstract

Untitled

Cited by 49 publications

References 36 publications

Human DDX3 Interacts with the HIV-1 Tat Protein to Facilitate Viral mRNA Translation

Human DDX3 Interacts with the HIV-1 Tat Protein to Facilitate Viral mRNA Translation

Association of RNA Helicase A with Human Immunodeficiency Virus Type 1 Particles

The DDX3 Subfamily of the DEAD Box Helicases: Divergent Roles as Unveiled by Studying Different Organisms and In Vitro Assays

Contact Info

Product

Resources

About