scholarly journals The exon junction complex core factor eIF4A3 is a key regulator of HPV16 gene expression

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Koceila Meznad ◽  
Philippe Paget-Bailly ◽  
Elise Jacquin ◽  
Anne Peigney ◽  
François Aubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Exon Junction Complex ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Exon Junction ◽  
Complex Core ◽  
Eukaryotic Translation Initiation ◽  
E6 And E7

Abstract High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas (HNSCCs). Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.

scholarly journals Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia

2005 ◽  
Vol 22 (3) ◽  
pp. 292-307 ◽  
Author(s):  
Chenhao Fan ◽  
Dumitru A. Iacobas ◽  
Dan Zhou ◽  
Qiaofang Chen ◽  
James K. Lai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Intermittent Hypoxia ◽  
Molecular Mechanisms ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Phenotypic Characterization ◽  
Mouse Heart ◽  
Eukaryotic Translation ◽  
Protein Levels

Chronic constant hypoxia (CCH), such as in pulmonary diseases or high altitude, and chronic intermittent hypoxia (CIH), such as in sleep apnea, can lead to major changes in the heart. Molecular mechanisms underlying these cardiac alterations are not well understood. We hypothesized that changes in gene expression could help to delineate such mechanisms. The current study used a neonatal mouse model in CCH or CIH combined with cDNA microarrays to determine changes in gene expression in the CCH or CIH mouse heart. Both CCH and CIH induced substantial alterations in gene expression. In addition, a robust right ventricular hypertrophy and cardiac enlargement was found in CCH- but not in CIH-treated mouse heart. On one hand, upregulation in RNA and protein levels of eukaryotic translation initiation factor-2α and -4E (eIF-2α and eIF-4E) was found in CCH, whereas eIF-4E was downregulated in 1- and 2-wk CIH, suggesting that eIF-4E is likely to play an important role in the cardiac hypertrophy observed in CCH-treated mice. On the other hand, the specific downregulation of heart development-related genes (e.g., notch gene homolog-1, MAD homolog-4) and the upregulation of proteolysis genes (e.g., calpain-5) in the CIH heart can explain the lack of hypertrophy in CIH. Interestingly, apoptosis was enhanced in CCH but not CIH, and this was correlated with an upregulation of proapoptotic genes and downregulation of anti-apoptotic genes in CCH. In summary, our results indicate that 1) the pattern of gene response to CCH is different from that of CIH in mouse heart, and 2) the identified expression differences in certain gene groups are helpful in dissecting mechanisms responsible for phenotypes observed.

scholarly journals Global Gene Expression Profiling Reveals Widespread yet Distinctive Translational Responses to Different Eukaryotic Translation Initiation Factor 2B-Targeting Stress Pathways

2005 ◽  
Vol 25 (21) ◽  
pp. 9340-9349 ◽  
Author(s):  
Julia B. Smirnova ◽  
Julian N. Selley ◽  
Fatima Sanchez-Cabo ◽  
Kathleen Carroll ◽  
A. Alan Eddy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Translation Initiation ◽  
Translational Control ◽  
Stress Conditions ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

ABSTRACT Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

scholarly journals The Human Cathelicidin Antimicrobial Peptide LL-37 Promotes the Growth of the Pulmonary PathogenAspergillus fumigatus

2018 ◽  
Vol 86 (7) ◽  
Author(s):  
Gerard Sheehan ◽  
Gudmundur Bergsson ◽  
Noel G. McElvaney ◽  
Emer P. Reeves ◽  
Kevin Kavanagh
Keyword(s):  
Antimicrobial Peptide ◽  
Fungal Growth ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Control Treatment ◽  
Content Type ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Eukaryotic Translation Initiation ◽  
Tissue Degradation

ABSTRACTThe pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the cathelicidin antimicrobial peptide LL-37, and the aim of this work was to assess the effect of LL-37 on the growth ofAspergillus fumigatus, a common pathogen of CF patients. Exposure ofA. fumigatusto LL-37 and its derived fragment RK-31 (1.95 μg/ml) for 24 h had a positive effect on growth (199.94% ± 6.172% [P< 0.05] and 218.20% ± 4.63% [P< 0.05], respectively), whereas scrambled LL-37 peptide did not (85.12% ± 2.92%). Exposure of mycelium (preformed for 24 h) to 5 μg/ml intact LL-37 for 48 h increased hyphal wet weight (4.37 ± 0.23 g,P< 0.001) compared to the control (2.67 ± 0.05 g) and scrambled LL-37 (2.23 ± 0.09 g) treatments. Gliotoxin secretion from LL-37 exposed hyphae (169.1 ± 6.36 ng/mg hyphae,P< 0.05) was increased at 24 h compared to the results seen with the control treatment (102 ± 18.81 ng/mg hyphae) and the scrambled LL-37 treatment (96.09 ± 15.15 ng/mg hyphae). Shotgun proteomic analysis of 24-h LL-37-treated hyphae revealed an increase in the abundance of proteins associated with growth (eukaryotic translation initiation factor 5A [eIF-5A] [16.3-fold increased]), tissue degradation (aspartic endopeptidase [4.7-fold increased]), and allergic reactions (Asp F13 [10-fold increased]). By 48 h, there was an increase in protein levels indicative of cellular stress (glutathione peroxidase [9-fold increased]), growth (eIF-5A [6-fold increased]), and virulence (RNase mitogillin [3.7-fold increased]). These results indicate that LL-37 stimulatesA. fumigatusgrowth and that this stimulation can result in increased fungal growth and secretion of toxins in the lungs of CF patients.

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