Targeting the ATP-dependent formation of herpesvirus ribonucleoprotein particle assembly as an antiviral approach

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

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Cotranscriptional Recruitment of RNA Exosome Cofactors Rrp47p and Mpp6p and Two Distinct Trf-Air-Mtr4 Polyadenylation (TRAMP) Complexes Assists the Exonuclease Rrp6p in the Targeting and Degradation of an Aberrant Messenger Ribonucleoprotein Particle (mRNP) in Yeast

Journal of Biological Chemistry ◽

10.1074/jbc.m113.491290 ◽

2013 ◽

Vol 288 (44) ◽

pp. 31816-31829 ◽

Cited By ~ 17

Author(s):

Igor Stuparevic ◽

Christine Mosrin-Huaman ◽

Nadège Hervouet-Coste ◽

Mateja Remenaric ◽

A. Rachid Rahmouni

Keyword(s):

Ribonucleoprotein Particle ◽

Messenger Ribonucleoprotein ◽

Rna Exosome

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Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly

Journal of Virology ◽

10.1128/jvi.79.23.14498-14506.2005 ◽

2005 ◽

Vol 79 (23) ◽

pp. 14498-14506 ◽

Cited By ~ 32

Author(s):

Ayna Alfadhli ◽

Tenzin Choesang Dhenub ◽

Amelia Still ◽

Eric Barklis

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Protein Assembly ◽

Particle Assembly ◽

Gag Protein ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Terminal Domains

ABSTRACT The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.

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