scholarly journals Review of Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Jiao Wei ◽  
Aimin Hui
Keyword(s):  
Immune Responses ◽  
Mrna Translation ◽  
Cellular Protein ◽  
Nonstructural Proteins ◽  
Design Features ◽  
Translational Activity ◽  
Ribosomal Function ◽  
Cellular Machinery ◽  
Successful Replication ◽  
Cellular Protein Synthesis

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine’s efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus’ genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.

scholarly journals Structural Basis for Competitive Inhibition of eIF4G-Mnk1 Interaction by the Adenovirus 100-Kilodalton Protein

2004 ◽  
Vol 78 (14) ◽  
pp. 7707-7716 ◽  
Author(s):  
Rafael Cuesta ◽  
Qiaoran Xi ◽  
Robert J. Schneider
Keyword(s):  
Protein Synthesis ◽  
Competitive Inhibition ◽  
Late Phase ◽  
Mrna Translation ◽  
Cellular Protein ◽  
Structural Basis ◽  
Binding Motif ◽  
Amino Acid Peptide ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

ABSTRACT Translation of most cellular mRNAs involves cap binding by the translation initiation complex. Among this complex of proteins are cap-binding protein eIF4E and the eIF4E kinase Mnk1. Cap-dependent mRNA translation generally correlates with Mnk1 phosphorylation of eIF4E when both are bound to eIF4G. During the late phase of adenovirus (Ad) infection translation of cellular mRNA is inhibited, which correlates with displacement of Mnk1 from eIF4G by the viral 100-kDa (100K) protein and dephosphorylation of eIF4E. Here we describe the molecular mechanism for 100K protein displacement of Mnk1 from eIF4G and elucidate a structural basis for eIF4G interaction with Mnk1 and 100K proteins and Ad inhibition of cellular protein synthesis. The eIF4G-binding site is located in an N-terminal 66-amino-acid peptide of 100K which is sufficient to bind eIF4G, displace Mnk1, block eIF4E phosphorylation, and inhibit eIF4F (cap)-dependent cellular mRNA translation. Ad 100K and Mnk1 proteins possess a common eIF4G-binding motif, but 100K protein binds more strongly to eIF4G than does Mnk1. Unlike Mnk1, for which binding to eIF4G is RNA dependent, competitive binding by 100K protein is RNA independent. These data support a model whereby 100K protein blocks cellular protein synthesis by coopting eIF4G and cap-initiation complexes regardless of their association with mRNA and displacing or blocking binding by Mnk1, which occurs only on preassembled complexes, resulting in dephosphorylation of eIF4E.

scholarly journals RNA viruses and microRNAs: challenging discoveries for the 21st century

2013 ◽  
Vol 45 (22) ◽  
pp. 1035-1048 ◽  
Author(s):  
Gokul Swaminathan ◽  
Julio Martin-Garcia ◽  
Sonia Navas-Martin
Keyword(s):  
Immune Responses ◽  
Rna Viruses ◽  
Cellular Protein ◽  
Host Cells ◽  
Dna Viruses ◽  
The Past ◽  
Complex Interactions ◽  
Viral Interactions ◽  
Cellular Machinery ◽  
Productive Replication

RNA viruses represent the predominant cause of many clinically relevant viral diseases in humans. Among several evolutionary advantages acquired by RNA viruses, the ability to usurp host cellular machinery and evade antiviral immune responses is imperative. During the past decade, RNA interference mechanisms, especially microRNA (miRNA)-mediated regulation of cellular protein expression, have revolutionized our understanding of host-viral interactions. Although it is well established that several DNA viruses express miRNAs that play crucial roles in their pathogenesis, expression of miRNAs by RNA viruses remains controversial. However, modulation of the miRNA machinery by RNA viruses may confer multiple benefits for enhanced viral replication and survival in host cells. In this review, we discuss the current literature on RNA viruses that may encode miRNAs and the varied advantages of engineering RNA viruses to express miRNAs as potential vectors for gene therapy. In addition, we review how different families of RNA viruses can alter miRNA machinery for productive replication, evasion of antiviral immune responses, and prolonged survival. We underscore the need to further explore the complex interactions of RNA viruses with host miRNAs to augment our understanding of host-virus interplay.

4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle

2000 ◽  
Vol 279 (4) ◽  
pp. E715-E729 ◽  
Author(s):  
O. Jameel Shah ◽  
Joshua C. Anthony ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson
Keyword(s):  
Translational Control ◽  
Mrna Translation ◽  
Cellular Protein ◽  
Initiation Factor ◽  
Translational Repressor ◽  
Initiation Factors ◽  
Initiation Phase ◽  
Eukaryotic Initiation Factor 4E ◽  
Integration Sites ◽  
A Site

Maintenance of cellular protein stores in skeletal muscle depends on a tightly regulated synthesis-degradation equilibrium that is conditionally modulated under an extensive range of physiological and pathophysiological circumstances. Recent studies have established the initiation phase of mRNA translation as a pivotal site of regulation for global rates of protein synthesis, as well as a site through which the synthesis of specific proteins is controlled. The protein synthetic pathway is exquisitely sensitive to the availability of hormones and nutrients and employs a comprehensive integrative strategy to interpret the information provided by hormonal and nutritional cues. The translational repressor, eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and the 70-kDa ribosomal protein S6 kinase (S6K1) have emerged as important components of this strategy, and together they coordinate the behavior of both eukaryotic initiation factors and the ribosome. This review discusses the role of 4E-BP1 and S6K1 in translational control and outlines the mechanisms through which hormones and nutrients effect changes in mRNA translation through the influence of these translational effectors.

scholarly journals Tumor-Progressive Mechanisms Mediating miRNA–Protein Interaction

2021 ◽  
Vol 22 (22) ◽  
pp. 12303
Author(s):  
Hiroaki Konishi ◽  
Hiroki Sato ◽  
Kenji Takahashi ◽  
Mikihiro Fujiya
Keyword(s):  
Cancer Progression ◽  
Regulatory System ◽  
Mrna Translation ◽  
Cellular Protein ◽  
Clinical Applications ◽  
Cancer Prognosis ◽  
Cellular Functions ◽  
Previous Decade ◽  
Extracellular Mirnas ◽  
Development And Differentiation

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA–protein systems in cancer progression and its future applications in cancer treatment.

Le transport de la phénylalanine et de la tyrosine chez Brevibacterium linens : spécificité et incorporation dans les protéines

1984 ◽  
Vol 30 (4) ◽  
pp. 430-438 ◽  
Author(s):  
P. Boyaval ◽  
Evelyne Moreira ◽  
M. J. Desmazeaud
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Cellular Protein ◽  
Cellular Proteins ◽  
Resting Cells ◽  
Brevibacterium Linens ◽  
Competitive Inhibitors ◽  
High Concentrations ◽  
Cellular Protein Synthesis

The specificity of phenylalanine and tyrosine carriers was investigated using actively metabolizing cells of Brevibacterium linens. The cellular protein synthesis of resting cells was very weakly inhibited, even with high concentrations of chloramphenicol or tetracycline. The nonaromatic amino acids were weak inhibitors for these carriers, while fluorinated analogues of phenylalanine and tyrosine were very potent competitive inhibitors. In practice these analogues cannot be used to replace amino acids to evaluate transport without incorporation because they are incorporated in cellular proteins.

Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination

1983 ◽  
Vol 3 (7) ◽  
pp. 1212-1221 ◽  
Author(s):  
A Babich ◽  
L T Feldman ◽  
J R Nevins ◽  
J E Darnell ◽  
C Weinberger
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Host Protein ◽  
Cell Protein ◽  
Viral Mrna ◽  
Initiation Of Translation ◽  
Viral Mutant ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

We have studied the adenovirus-induced inhibition of host cell protein synthesis and the effect of infection on the overall metabolism of host cell mRNA during the late phase of adenovirus infection by following the fate of a number of cellular mRNAs complementary to specific cloned DNA segments. At a time in infection when the rate of total cellular protein synthesis is drastically (greater than 90%) reduced, transcription of specific cellular genes is undiminished. However, the transport of newly synthesized cellular mRNA to the cytoplasm is greatly decreased. This decreased appearance of new mRNA in the cytoplasm cannot account for the observed cessation of cell specific protein synthesis, however, since the concentration of several preexisting cellular mRNAs, including the mRNA for actin, remains unchanged throughout the course of infection. The preexisting mRNA is intact, capped, and functional as judged by its ability to direct protein synthesis in vitro in a cap-dependent fashion. The interruption in host translation appears to operate at the level of initiation directly, since we find that fewer ribosomes are associated with a given cellular mRNA after infection than before infection. Furthermore, the in vivo inhibition of cellular protein synthesis does not appear to be the result of competition with viral mRNA, since conditions which prevent the efficient initiation of translation of viral mRNA (infection with a viral mutant) do not result in the recovery of cell translation. Thus, it appears that a late adenovirus gene product directly mediates a shutoff of host protein synthesis.

Normal Cellular Protein Synthesis and Heat Shock

1994 ◽  
pp. 61-76 ◽  
Author(s):  
Mark R. Brodl ◽  
Jacqueline D. Campbell ◽  
Kent K. Grindstaff ◽  
Lora Fielding
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Cellular Protein ◽  
Cellular Protein Synthesis
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