scholarly journals Focus on Translation Initiation of the HIV-1 mRNAs

2018 ◽  
Vol 20 (1) ◽  
pp. 101 ◽  
Author(s):  
Sylvain de Breyne ◽  
Théophile Ohlmann
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cellular Proteins ◽  
Internal Ribosome Entry ◽  
Eukaryotic Translation ◽  
Cellular Environment ◽  
Key Steps ◽  
Hiv 1

To replicate and disseminate, viruses need to manipulate and modify the cellular machinery for their own benefit. We are interested in translation, which is one of the key steps of gene expression and viruses that have developed several strategies to hijack the ribosomal complex. The type 1 human immunodeficiency virus is a good paradigm to understand the great diversity of translational control. Indeed, scanning, leaky scanning, internal ribosome entry sites, and adenosine methylation are used by ribosomes to translate spliced and unspliced HIV-1 mRNAs, and some require specific cellular factors, such as the DDX3 helicase, that mediate mRNA export and translation. In addition, some viral and cellular proteins, including the HIV-1 Tat protein, also regulate protein synthesis through targeting the protein kinase PKR, which once activated, is able to phosphorylate the eukaryotic translation initiation factor eIF2α, which results in the inhibition of cellular mRNAs translation. Finally, the infection alters the integrity of several cellular proteins, including initiation factors, that directly or indirectly regulates translation events. In this review, we will provide a global overview of the current situation of how the HIV-1 mRNAs interact with the host cellular environment to produce viral proteins.

scholarly journals Established and Emerging Regulatory Roles of Eukaryotic Translation Initiation Factor 5B (eIF5B)

2021 ◽  
Vol 12 ◽  
Author(s):  
Prakash Amruth Raj Chukka ◽  
Stacey D. Wetmore ◽  
Nehal Thakor
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Translational Regulation ◽  
Eukaryotic Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Cellular Mrnas ◽  
Eukaryotic Translation Initiation ◽  
Initiation Stage

Translational control (TC) is one the crucial steps that dictate gene expression and alter the outcome of physiological process like programmed cell death, metabolism, and proliferation in a eukaryotic cell. TC occurs mainly at the translation initiation stage. The initiation factor eIF5B tightly regulates global translation initiation and facilitates the expression of a subset of proteins involved in proliferation, inhibition of apoptosis, and immunosuppression under stress conditions. eIF5B enhances the expression of these survival proteins to allow cancer cells to metastasize and resist chemotherapy. Using eIF5B as a biomarker or drug target could help with diagnosis and improved prognosis, respectively. To achieve these goals, it is crucial to understand the role of eIF5B in translational regulation. This review recapitulates eIF5B’s regulatory roles in the translation initiation of viral mRNA as well as the cellular mRNAs in cancer and stressed eukaryotic cells.

Abstract 321: Deletion Of The Translational Repressors Eukaryotic Translation Initiation Factor 4e Binding Proteins 1 And 2 Protects Against Pressure Overload Induced Heart Failure

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
zhongbing lu ◽  
Xinli Hu ◽  
Yimin Huang ◽  
Xin Xu ◽  
Ping zhang ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Binding Proteins ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Double Knockout ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

Assembly of the translation initiation machinery is negatively regulated by the eukaryotic translation initiation factor 4E binding proteins, which sequester the mRNA cap-binding protein eIF4E, thus preventing assembly of an intact initiation complex. However, the role of translational control on the development of congestive heart failure (CHF) has not been systematically examined. Here we perturbed translational control in mice by knockout of both 4E binding protein 1 (Eif4ebp1) and 2 (Eif4ebp2) (designated as Eif4ebp1/2 double knockout) to study its impact on left ventricular hypertrophy and CHF resulting from transverse aortic constriction. Eif4ebp1/2 double knockout caused a modest increase in left ventricular mass under basal conditions. However, following transverse aortic constriction, Eif4ebp1/2 double knockout profoundly attenuated the development of CHF and its attendant mortality. Examination of candidate genes involved in the mechanism revealed increased expression of transcription factors for genes governing energy metabolism and mitochondrial biogenesis with corresponding increases in the expression of their target genes. Our data indicate that removing physiological restraints on translation initiation exerts a profound cardiac protective effect against pressure overload induced CHF, suggesting that method(s) to disrupt the function of the 4E binding proteins may be a novel therapeutic approach for preventing or treating CHF.

Translational control of the cdc25 cell cycle phosphatase: a molecular mechanism coupling mitosis to cell growth

1999 ◽  
Vol 112 (18) ◽  
pp. 3137-3146 ◽  
Author(s):  
R.R. Daga ◽  
J. Jimenez
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Translational Control ◽  
Cell Mass ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Mrnas ◽  
Eukaryotic Translation Initiation ◽  
Yeast Mutants

The eukaryotic translation initiation factor 4A (eIF4A) is an RNA helicase required for translation initiation of eukaryotic mRNAs. By engineering fission yeast mutants with diminished eIF4A activity, we have found that translation of cdc25 mRNAs (a dosage-dependent activator of mitosis in all eukaryotic cells) is particularly sensitive to limitations of protein synthesis mediated by limited eIF4A activity. Genetic and biochemical analysis indicated that a rate-limited translation initiation of cdc25 mRNAs, exerted throughout its unusual 5′ untranslated leader, acts as a molecular sensor to ensure that a minimum cell mass (protein synthesis) is attained before mitosis occurs. The Cdc13 cyclin B is also among the limited pool of proteins whose translation is sensitive to reduced translation initiation activity. Interestingly, the 5′ leader sequences of cdc25 and cdc13 mRNAs have conserved features which are unusual in other yeast mRNAs, suggesting that common mechanisms operate in the expression of these two key mitotic activators at the translational level.

scholarly journals Human eIF3: from ‘blobology’ to biological insight

2017 ◽  
Vol 372 (1716) ◽  
pp. 20160176 ◽  
Author(s):  
Jamie H. D. Cate
Keyword(s):  
Translation Initiation ◽  
Molecular Mechanisms ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Messenger Rnas ◽  
Internal Ribosome Entry ◽  
General Role ◽  
Eukaryotic Translation ◽  
Biological Insight ◽  
Eukaryotic Translation Initiation

Translation in eukaryotes is highly regulated during initiation, a process impacted by numerous readouts of a cell's state. There are many cases in which cellular messenger RNAs likely do not follow the canonical ‘scanning’ mechanism of translation initiation, but the molecular mechanisms underlying these pathways are still being uncovered. Some RNA viruses such as the hepatitis C virus use highly structured RNA elements termed internal ribosome entry sites (IRESs) that commandeer eukaryotic translation initiation, by using specific interactions with the general eukaryotic translation initiation factor eIF3. Here, I present evidence that, in addition to its general role in translation, eIF3 in humans and likely in all multicellular eukaryotes also acts as a translational activator or repressor by binding RNA structures in the 5′-untranslated regions of specific mRNAs, analogous to the role of the mediator complex in transcription. Furthermore, eIF3 in multicellular eukaryotes also harbours a 5′ 7-methylguanosine cap-binding subunit—eIF3d—which replaces the general cap-binding initiation factor eIF4E in the translation of select mRNAs. Based on results from cell biological, biochemical and structural studies of eIF3, it is likely that human translation initiation proceeds through dozens of different molecular pathways, the vast majority of which remain to be explored. This article is part of the themed issue ‘Perspectives on the ribosome’.

scholarly journals Eukaryotic Translation Initiation Factor 5 Is Critical for Integrity of the Scanning Preinitiation Complex and Accurate Control of GCN4 Translation

2005 ◽  
Vol 25 (13) ◽  
pp. 5480-5491 ◽  
Author(s):  
Chingakham Ranjit Singh ◽  
Cynthia Curtis ◽  
Yasufumi Yamamoto ◽  
Nathan S. Hall ◽  
Dustin S. Kruse ◽  
...  
Keyword(s):  
Amino Acid ◽  
Translation Initiation ◽  
Translational Control ◽  
Point Mutations ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Preinitiation Complex ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

ABSTRACT The integrity of eukaryotic translation initiation factor (eIF) interactions in ribosomal preinitiation complexes is critical for the proper regulation of GCN4 mRNA translation in response to amino acid availability. Increased phosphorylation of eIF2 under amino acid starvation conditions leads to a corresponding increase in GCN4 mRNA translation. The carboxyl-terminal domain (CTD) of eIF5 (eIF5-CTD) has been identified as a potential nucleation site for preinitiation complex assembly. To further characterize eIF5 and delineate its role in GCN4 translational control, we isolated mutations leading to temperature sensitivity (Ts− phenotype) targeted at TIF5, the structural gene encoding eIF5 in yeast (Saccharomyces cerevisiae). Nine single point mutations were isolated, in addition to an allele in which the last 15 amino acids were deleted. The nine point mutations clustered in the eIF5-CTD, which contains two conserved aromatic/acidic boxes. Six of the point mutations derepressed GCN4 translation independent of eIF2 phosphorylation (Gcd− phenotype) at a permissive temperature, directly implicating eIF5-CTD in the eIF2/GTP/Met-tRNAi Met ternary complex binding process required for GCN4 translational control. In addition, stronger restriction of eIF5-CTD function at an elevated temperature led to failure to derepress GCN4 translation (Gcn− phenotype) in all of the mutants, most likely due to leaky scanning of the first upstream open reading frame of GCN4 mRNA. This latter result directly implicates eIF5-CTD in the process of accurate scanning for, or recognition of, AUG codons. Taken together, our results indicate that eIF5-CTD plays a critical role in both the assembly of the 43S complex and the postassembly process in the 48S complex, likely during the scanning process.

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