The Heterogeneous Nuclear Ribonucleoprotein K (hnRNP K) Interacts with Dengue Virus Core Protein

Chang, Ching-Jin; Luh, Hui-Wen; Wang, Shao–Hung; Lin, Hui-Jin; Lee, Sheng-Chung; Hu, Shiau-Ting

doi:10.1089/104454901317094981

Cited by 69 publications

(59 citation statements)

References 44 publications

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“…Poly(U) decreased the interaction of YB-1 with hnRNP K, whereas the other polynucleotides had no effect (30). Previously, we also reported that the interaction between hnRNP K and the dengue virus core protein was altered in the presence of poly(C) and poly(U) (32). Fig.…”

Section: Discussionmentioning

confidence: 50%

An RNA Helicase, DDX1, Interacting with Poly(A) RNA and Heterogeneous Nuclear Ribonucleoprotein K

Chen

Lin

Tsay

et al. 2002

Journal of Biological Chemistry

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Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multifunctional protein known to be involved in the regulation of transcription, translation, nuclear transport, and signal transduction. To systematically obtain insight into mechanisms of hnRNP K activities, we set out to identify protein factors that interact with hnRNP K by using glutathione S-transferase-hnRNP K affinity chromatography followed by liquid chromatography/mass spectrometry/mass spectrometry analysis. Several partner proteins in the K562 cell lysates were identified through this method. One of them is a DEAD box-containing putative RNA helicase, DDX1. In vitro binding and co-immunoprecipitation studies confirmed the protein-protein interaction between hnRNP K with DDX1, and the region spanning amino acids 1-276 of hnRNP K is apparently responsible for its physical interaction with DDX1. Interestingly, their interaction was disrupted by the addition of poly(C), poly(A), and poly(U) RNA substrates. We found that DDX1 was a homopolymeric poly(A) RNA-binding protein. On the other hand, the ATPase activity of the purified recombinant DDX1 protein was stimulated by these homopolymeric RNAs and yeast total RNA but not by DNA. Moreover, the immunoprecipitated DDX1 complex but not purified DDX1 can unwind double-stranded RNA having singlestranded poly(A) overhangs.The hnRNP K 1 protein has been identified as a component of the heterogeneous nuclear ribonucleoprotein complexes. These hnRNP proteins bind pre-mRNAs directly and appear to facilitate various stages of mRNA biogenesis (1-3). hnRNP K can bind to RNA and single-stranded or double-stranded DNA. The nucleic acid binding activity of hnRNP K is mediated by three repeats of motifs termed the K homology domain, which consists of 65-70 residues (4). It contains both classical nuclear localization signal and the K nuclear shuttling domain that allow the protein to shuttle between nucleus and cytoplasm (5). hnRNP K appears to be involved in transcriptional regulation as exemplified by its binding to a C-rich sequence (the CT element) within the human c-myc promoter and subsequent activation of c-myc expression (6 -8). Additionally, its association with CCAAT/enhancer-binding protein ␤ results in the repression of CCAAT/enhancer-binding protein ␤ target genes (9). hnRNP K was also reported to bind 3Ј end of 15-lipoxygenase, and HPV 16 L2 mRNA was reported to trigger translation inhibition (10, 11). Moreover, direct protein-protein interactions between hnRNP K and some proto-oncogene products serve as clear evidence that hnRNP K acts as a docking platform to facilitate molecular interactions within signal transduction cascades (12-16).Modulation of RNA structure is an essential step in many fundamental cellular processes, including RNA synthesis, splicing, export, turnover, and translation. Recently, an increasing number of RNA helicases from different organisms, ranging from bacteria to yeast, human, and virus, has been identified (17, 18). DEAD box proteins are a family of putative RNA helicases t...

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Section: Discussionmentioning

confidence: 50%

An RNA Helicase, DDX1, Interacting with Poly(A) RNA and Heterogeneous Nuclear Ribonucleoprotein K

Chen

Lin

Tsay

et al. 2002

Journal of Biological Chemistry

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“…The role of the C protein in the nucleus has not yet been elucidated. However, it has been shown to interact with a number of (predominantly nuclear) host proteins, including hnRNP-K, DAXX, and Core histones (26)(27)(28)(29)(30). The cellular protein nucleolin (NCL) is found primarily within the nucleolus but can also be found in the cytoplasm and on the plasma membrane (31)(32)(33).…”

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confidence: 99%

Nucleolin Interacts with the Dengue Virus Capsid Protein and Plays a Role in Formation of Infectious Virus Particles

Balinsky

Schmeisser

Ganesan

et al. 2013

J Virol

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Dengue virus (DENV), a member of the genus Flavivirus, causes a spectrum of disease in humans that can range from a mild febrile illness to potentially fatal hemorrhage or shock syndromes. Four serotypes of DENV (DENV-1, -2, -3, and -4) are transmitted by the bite of a mosquito vector and are responsible for more than 50 million infections each year. Infection with one DENV serotype does not confer lasting immunity to the others (1-3). The most severe clinical manifestations of dengue are associated with secondary infections by a heterologous DENV serotype (2). Increasing urbanization, cocirculation of multiple DENV serotypes within the same geographic area, and expansion of its insect vector contribute to the increasing importance of dengue to global health (2, 3).DENV contains a positive-sense single-stranded RNA (ssRNA) genome that is translated as a single open reading frame. The resulting polyprotein is cleaved by virus and host proteases into three structural and at least seven nonstructural proteins (4, 5). The capsid (C) protein functions as a structural component of the DENV virion, encapsulating the ssRNA genome of the virus (4, 5). The DENV C protein is composed of four alpha helices with an unstructured amino terminus and forms antiparallel homodimers.

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“…28 The function of the C protein in the nucleus remains to be investigated, but it has been hypothesized that the DENV C protein services as a transcription modulator similar to the core protein of hepatitis C virus, 9 which is involved in regulating the life cycle of DENV and is a building block of the virus. 30 The hepatitis C virus core protein has been shown to interact with the transcription factor hnRNP K, which is located in the nucleus 31 and is known to enhance c-Myc to promote apoptosis. 32 It is possible that DENV C protein also modulates apoptosis of host cells, leading to the development of disease.…”

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Comparative Analysis of Full-Length Genomic Sequences of 10 Dengue Serotype 1 Viruses Associated with Different Genotypes, Epidemics, and Disease Severity Isolated in Thailand over 22 Years

Tang

Rodpradit²,

Chinnawirotpisan³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Abstract. Comparative sequence analysis was performed on the full-length genomic sequences of 10 representative dengue virus serotype 1 (DENV-1) strains sampled from patients at Children's Hospital, Bangkok, Thailand over a 22-year period, which represented different epidemics, disease severity, and sampling time. The results showed remarkable inter-genotypic variation between predominant and non-predominant genotypes and genotype-specific amino acids and nucleotides throughout the entire viral genome except for the 5′-non-translated region. The frequency of intra-genotypic variation was correlated with dengue transmission rate and sampling time. The 5′-non-translated region of all 10 viruses was highly conserved for predominant and non-predominant genotypes and NS2B was the most conserved protein. Some intra-genotypic substitutions of amino acids and nucleotides in predominant genotype strains were fixed in the viral genome since 1994, which indicated that the evolution of predominant genotype strains in situ over time might contribute to increased virus fitness important for sustaining dengue epidemics in Thailand.

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The Heterogeneous Nuclear Ribonucleoprotein K (hnRNP K) Interacts with Dengue Virus Core Protein

Cited by 69 publications

References 44 publications

An RNA Helicase, DDX1, Interacting with Poly(A) RNA and Heterogeneous Nuclear Ribonucleoprotein K

An RNA Helicase, DDX1, Interacting with Poly(A) RNA and Heterogeneous Nuclear Ribonucleoprotein K

Nucleolin Interacts with the Dengue Virus Capsid Protein and Plays a Role in Formation of Infectious Virus Particles

Comparative Analysis of Full-Length Genomic Sequences of 10 Dengue Serotype 1 Viruses Associated with Different Genotypes, Epidemics, and Disease Severity Isolated in Thailand over 22 Years

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