Cooperative binding of the hnRNP K three KH domains to mRNA targets

Paziewska, Agnieszka; Wyrwicz, Lucjan; Bujnicki, Janusz M.; Bomsztyk, Karol; Ostrowski, Jerzy

doi:10.1016/j.febslet.2004.08.086

Cited by 57 publications

(45 citation statements)

References 40 publications

(88 reference statements)

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“…K protein binding to RNA reflects synergistic interaction between three KH domains and cognate RNA where each KH domain binds one of three C-rich boxes (Paziewska et al, 2004). As shown in Figure 3, the structural changes resulting from the putative phosphorylation of Thr92 does not disrupt the 3D-fold of the KH domain (panels A -C).…”

Section: Resultsmentioning

confidence: 96%

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

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The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding protein involved in many processes that compose gene expression. K protein is upregulated in the malignant processes and has been shown to modulate the expression of genes involved in mitogenic responses and tumorigenesis. To explore the possibility that there are alternative isoforms of K protein expressed in colon cancer, we amplified and sequenced K protein mRNA that was isolated from colorectal cancers as well as from normal tissues surrounding the tumours. Sequencing revealed a single G-to-A base substitution at position 274 that was found in tumours and surrounding mucosa, but not in individuals that had no colorectal tumour. This substitution most likely reflects an RNA editing event because it was not found in the corresponding genomic DNAs. Sequencing of RNA from normal colonic mucosa of patients with prior resection of colorectal cancer revealed only the wild-type K protein transcript, indicating that G274A isoform is tumour related. To our knowledge, this is the first example of an RNA editing event in cancer and its surrounding tissue, a finding that may offer a new diagnostic and treatment marker.

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Section: Resultsmentioning

confidence: 96%

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

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“…Data depicted are representative of at least two independent experiments lysates ( Figure 2b) as compared with recombinant purified hnRNP K (Figure 2c), suggesting that cellular factors contribute to this proteolysis. Because hnRNP K is an RNA-interacting protein, 24,25 the effects of RNA on GrMmediated hnRNP K cleavage were examined. Cell lysates were preincubated with or without RNase, followed by GrM treatment.…”

Section: Resultsmentioning

confidence: 99%

“…32,33 Binding of hnRNP K to RNA is mediated by three KH domains within hnRNP K that act synergistically to provide both high-affinity binding and specificity (Figure 2). 24,25 Hence, loss of only a single KH domain dramatically reduces the RNA binding capacity of hnRNP K. 25 GrM cleaved hnRNP K at least at five independent sites, including Leu 125 , Leu 133 , and Met 359 , that are located in two apparent proteolysissensitive hot spots, thereby dissecting the functional KH domains (Figure 2). This strongly suggests that GrM abrogates the ability of hnRNP K to bind to IE2 mRNA, resulting in reduced IE2 protein expression and reduced HCMV replication.…”

Section: Discussionmentioning

confidence: 99%

Granzyme M targets host cell hnRNP K that is essential for human cytomegalovirus replication

et al. 2012

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Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and HCMV infection in immunocompromised patients may trigger devastating disease. Cytotoxic lymphocytes control HCMV by releasing granzymes towards virus-infected cells. In mice, granzyme M (GrM) has a physiological role in controlling murine CMV infection. However, the underlying mechanism remains poorly understood. In this study, we showed that human GrM was expressed by HCMV-specific CD8 þ T cells both in latently infected healthy individuals and in transplant patients during primary HCMV infection. We identified host cell heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a physiological GrM substrate. GrM most efficiently cleaved hnRNP K in the presence of RNA at multiple sites, thereby likely destroying hnRNP K function. Host cell hnRNP K was essential for HCMV replication not only by promoting viability of HCMV-infected cells but predominantly by regulating viral immediate-early 2 (IE2) protein levels. Furthermore, hnRNP K interacted with IE2 mRNA. Finally, GrM decreased IE2 protein expression in HCMV-infected cells. Our data suggest that targeting of hnRNP K by GrM contributes to the mechanism by which cytotoxic lymphocytes inhibit HCMV replication. This is the first evidence that cytotoxic lymphocytes target host cell proteins to control HCMV infections.

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“…Proper selection of the protein domain is necessary [102][103][104][105][106][107][108]. In addition to pure chemical data [109][110][111][112][113][114][115][116] in the context of the Drug Discovery [117][118][119][120][121][122][123][124][125][126][127], there is also a need for some knowledge on protein-protein interactions, the high quality structural prediction of proteins [2,[128][129][130][131][132][133][134][135][136] and their inhibitors, and a detailed understanding of how those inhibitors affect the molecular recognition between proteins. The development of theoretical methods for function annotation clearly shows that a detailed analysis of local characteristics of the protein chain can significantly improve accuracy.…”

Section: Resultsmentioning

confidence: 99%

The interactome: Predicting the protein-protein interactions in cells

Plewczyński

Ginalski

2009

Cellular and Molecular Biology Letters

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Abstract:The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.

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Cooperative binding of the hnRNP K three KH domains to mRNA targets

Cited by 57 publications

References 40 publications

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

Granzyme M targets host cell hnRNP K that is essential for human cytomegalovirus replication

The interactome: Predicting the protein-protein interactions in cells

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