Translational control of coronaviruses

Abstract Coronaviruses represent a large family of enveloped RNA viruses that infect a large spectrum of animals. In humans, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic and is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2002 and 2012, respectively. All viruses described to date entirely rely on the protein synthesis machinery of the host cells to produce proteins required for their replication and spread. As such, virus often need to control the cellular translational apparatus to avoid the first line of the cellular defense intended to limit the viral propagation. Thus, coronaviruses have developed remarkable strategies to hijack the host translational machinery in order to favor viral protein production. In this review, we will describe some of these strategies and will highlight the role of viral proteins and RNAs in this process.

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Regulation of translation initiation by herpesviruses

Biochemical Society Transactions ◽

10.1042/bst0360701 ◽

2008 ◽

Vol 36 (4) ◽

pp. 701-707 ◽

Cited By ~ 11

Author(s):

Richard W.P. Smith ◽

Sheila V. Graham ◽

Nicola K. Gray

Keyword(s):

Protein Synthesis ◽

Translational Control ◽

Translational Regulation ◽

Large Family ◽

Cell Protein ◽

Viral Protein Synthesis ◽

Viral Mrnas ◽

Dna Viruses ◽

Protein Synthesis Machinery ◽

Regulate Protein

Viruses are dependent upon the host cell protein synthesis machinery, thus they have developed a range of strategies to manipulate host translation to favour viral protein synthesis. Consequently, the study of viral translation has been a powerful tool for illuminating many aspects of cellular translational control. Although much work to date has focused on translational regulation by RNA viruses, DNA viruses have also evolved complex mechanisms to regulate protein synthesis. Here we summarize work on a large family of DNA viruses, the Herpesviridae, which have evolved mechanisms to sustain efficient cap-dependent translation and to regulate the translation of specific viral mRNAs.

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Translational Roles of Elongation Factor 2 Protein Lysine Methylation

Journal of Biological Chemistry ◽

10.1074/jbc.m114.605527 ◽

2014 ◽

Vol 289 (44) ◽

pp. 30511-30524 ◽

Cited By ~ 15

Author(s):

Maria C. Dzialo ◽

Kyle J. Travaglini ◽

Sean Shen ◽

Kevin Roy ◽

Guillaume F. Chanfreau ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Protein Synthesis ◽

Elongation Factor ◽

Amino Acid Sequences ◽

Fine Tuning ◽

Lysine Methylation ◽

Translational Machinery ◽

Elongation Factor 2 ◽

Translational Apparatus

Methylation of various components of the translational machinery has been shown to globally affect protein synthesis. Little is currently known about the role of lysine methylation on elongation factors. Here we show that in Saccharomyces cerevisiae, the product of the EFM3/YJR129C gene is responsible for the trimethylation of lysine 509 on elongation factor 2. Deletion of EFM3 or of the previously described EFM2 increases sensitivity to antibiotics that target translation and decreases translational fidelity. Furthermore, the amino acid sequences of Efm3 and Efm2, as well as their respective methylation sites on EF2, are conserved in other eukaryotes. These results suggest the importance of lysine methylation modification of EF2 in fine tuning the translational apparatus.

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Characterizing Cellular Responses During Oncolytic Maraba Virus Infection

International Journal of Molecular Sciences ◽

10.3390/ijms20030580 ◽

2019 ◽

Vol 20 (3) ◽

pp. 580 ◽

Cited By ~ 5

Author(s):

Golnoush Hassanzadeh ◽

Thet Naing ◽

Tyson Graber ◽

Seyed Jafarnejad ◽

David Stojdl ◽

...

Keyword(s):

High Selectivity ◽

Cellular Responses ◽

Oncolytic Viruses ◽

Host Cells ◽

End Joining ◽

Viral Propagation ◽

Infected Cells ◽

Translational Arrest ◽

Low Cytotoxicity

The rising demand for powerful oncolytic virotherapy agents has led to the identification of Maraba virus, one of the most potent oncolytic viruses from Rhabdoviridae family which displays high selectivity for killing malignant cells and low cytotoxicity in normal cells. Although the virus is readied to be used for clinical trials, the interactions between the virus and the host cells is still unclear. Using a newly developed interferon-sensitive mutant Maraba virus (MG1), we have identified two key regulators of global translation (4E-BP1 and eIF2α) as being involved in the regulation of protein synthesis in the infected cells. Despite the translational arrest upon viral stress, we showed an up-regulation of anti-apoptotic Bcl-xL protein that provides a survival benefit for the host cell, yet facilitates effective viral propagation. Given the fact that eIF5B canonically regulates 60S ribosome subunit end joining and is able to replace the role of eIF2 in delivering initiator tRNA to the 40S ribosome subunit upon the phosphorylation of eIF2α we have tested whether eIF5B mediates the translation of target mRNAs during MG1 infection. Our results show that the inhibition of eIF5B significantly down-regulates the level of Bcl-xL steady-state mRNA, thus indirectly attenuates viral propagation.

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Glucocorticoids oppose translational control by leucine in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.5.e1185 ◽

2000 ◽

Vol 279 (5) ◽

pp. E1185-E1190 ◽

Cited By ~ 43

Author(s):

O. Jameel Shah ◽

Joshua C. Anthony ◽

Scot R. Kimball ◽

Leonard S. Jefferson

Keyword(s):

Skeletal Muscle ◽

Translational Control ◽

Regulatory Element ◽

Mrna Translation ◽

Initiation Factor ◽

Protein Homeostasis ◽

S6 Kinase ◽

Translational Machinery ◽

Ribosomal Protein S6 ◽

Translational Apparatus

Glucocorticoids comprise an important class of hormonal mediators of fuel and protein homeostasis in normal and pathological scenarios. In skeletal muscle, exposure to glucocorticoids is characterized by a reduction in protein synthetic rate coincident with hampered translation initiation. However, it is unclear whether this involves attenuation of anabolic stimuli or is simply due to inhibition of the basally activated translational apparatus. Therefore, this inquiry was designed to determine whether leucine, administered orally, could rescue the translational inhibition induced by glucocorticoids. Dexamethasone, injected intraperitoneally, acutely diminished protein synthetic rates to 80% of control values in skeletal muscle from rat hindlimb. The eukaryotic initiation factor (eIF)4 regulatory element was simultaneously and negatively impacted via sequestration of eIF4E by the hypophosphorylated form of the translational suppressor, eIF4E binding protein 1 (4E-BP1). The 70-kDa ribosomal protein S6 kinase (S6K1) was also dephosphorylated, notably at T389, in response to glucocorticoids. Leucine, administered orally, effectively restored each aforementioned translational parameter to control levels. Inasmuch as leucine's potency in modulation of the translational machinery, and indeed of protein turnover in general, is widely appreciated, this amino acid may prove useful in normalizing the impairment of mRNA translation associated with various muscle-wasting pathologies, such as glucocorticoid excess.

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The role of family networks and social capital on women's fertility intentions in Ouagadougou, Burkina Faso

Journal of Demographic Economics ◽

10.1017/dem.2021.18 ◽

2021 ◽

pp. 1-19

Author(s):

Moussa Bougma ◽

Clémentine Rossier

Keyword(s):

Social Capital ◽

Extended Family ◽

Large Family ◽

Economic Resources ◽

High Fertility ◽

Family Networks ◽

Children's Schooling

Abstract Family solidarities remain strong in African societies. In Ouagadougou, transfers within extended family networks provide an omnipresent means for coping with life's difficulties, and the desired number of children remains relatively high. The role of family networks in maintaining high fertility is rarely studied however for lack of data in conventional demographic surveys. This study uses original retrospective data and logistic regression methods to explore the role of the extended family's social capital in shaping women's desire for children in Ouagadougou. Results show that women belong to three types of family networks: (1) women who belong to large family networks on both her own and her husband's side and who maintain a moderate number of close relations with their own relatives; (2) women who also belong to large family networks on both their and their husband's sides but who maintain a greater number of close relations with their own blood relatives; (3) unmarried women with relatives only on their side and numerous close relations with their family. Support for children's schooling comes more often from women's relatives in networks type 2 and 3, and from husbands' relatives in network type 1. Support for children's schooling increases with the level of economic resources in family networks (proxied by the presence of a public employee), in all network types. Women in type 2 networks (centered on women's relatives) are more likely to want additional children compared to women in type 1 networks (centered on their husband's relatives), after controlling for economic resources in networks. This result suggests that practical support provided by family members could play a role, on top of economic support, in encouraging high fertility in Ouagadougou.

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The potential role of Bromhexine in the management of COVID-19: Decipher and a real game-changer

CURRENT MEDICAL AND DRUG RESEARCH ◽

10.53517/cmdr.2581-5008.512021212 ◽

2021 ◽

Vol 5 (01) ◽

pp. 1-4

Author(s):

Hayder M. Al-Kuraishy ◽

Marwa S. Al-Niemi ◽

Nawar R. Hussain ◽

Ali I. Al-Gareeb ◽

Claire Lugnier

Keyword(s):

Potential Role ◽

Host Cells ◽

Bronchial Epithelial ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus ◽

Transmembrane Serine Protease ◽

Game Changer

Primary infection of SARS-CoV-2 (novel coronavirus or 2019-nCoV), which leads to Covid-19, targets specific cells, such as nasal, bronchial epithelial and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Also, type 2 transmembrane serine protease (TMPRSS2) present in the host cell promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells. One of the TMPRSS2 inhibitors with a greater distribution capacity into the lung tissue is bromhexine hydrochloride which attenuates the entry and proliferation of SARS-CoV-2. Bromhexine is an effective drug in the management and treatment of Covid-19 pneumonia via targeting ACE2/ TMPRSS2 pathway. However, prospective and controlled clinical trials are recommended to confirm this observation.

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Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.668500 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yu-Ju Liu ◽

Yijuang Chern

Keyword(s):

Neurodegenerative Diseases ◽

Translational Control ◽

Energy Homeostasis ◽

Protein Translation ◽

Translational Machinery ◽

Cellular Energy ◽

Mechanistic Target Of Rapamycin ◽

Translational Regulators ◽

Lateral Sclerosis

Impaired energy homeostasis and aberrant translational control have independently been implicated in the pathogenesis of neurodegenerative diseases. AMP kinase (AMPK), regulated by the ratio of cellular AMP and ATP, is a major gatekeeper for cellular energy homeostasis. Abnormal regulation of AMPK has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Most importantly, AMPK activation is known to suppress the translational machinery by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), activating translational regulators, and phosphorylating nuclear transporter factors. In this review, we describe recent findings on the emerging role of protein translation impairment caused by energy dysregulation in neurodegenerative diseases.

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The role of DUBs in the post-translational control of cell migration

Essays in Biochemistry ◽

10.1042/ebc20190022 ◽

2019 ◽

Vol 63 (5) ◽

pp. 579-594 ◽

Cited By ~ 2

Author(s):

Guillem Lambies ◽

Antonio García de Herreros ◽

Víctor M. Díaz

Keyword(s):

Cell Migration ◽

Translational Control ◽

Epithelial To Mesenchymal Transition ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Mesenchymal Transition ◽

Tgfβ Receptors ◽

Fundamental Process ◽

Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

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