Plant translation initiation factors: it is not easy to be green

2004 ◽  
Vol 32 (4) ◽  
pp. 589-591 ◽  
Author(s):  
K.S. Browning
Keyword(s):  
Translation Initiation ◽  
Binding Proteins ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Translational Machinery ◽  
Initiation Factors ◽  
Translation Initiation Factors

Plants have significant differences in some of the ‘parts’ of the translational machinery. There are two forms of eukaryotic initiation factor (eIF) 4F, eIF3 has two novel subunits, eIF4B is poorly conserved, and eIF2 kinases and eIF4E binding proteins (4E-BP) are yet to be discovered. These differences suggest that plants may regulate their translation in unique ways.

Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F

1990 ◽  
Vol 10 (3) ◽  
pp. 1134-1144 ◽  
Author(s):  
F Rozen ◽  
I Edery ◽  
K Meerovitch ◽  
T E Dever ◽  
W C Merrick ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Direct Evidence ◽  
Rna Helicase ◽  
Initiation Factor ◽  
Helicase Activity ◽  
Ribosome Binding ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Hydrolysis Of

The mechanism of ribosome binding to eucaryotic mRNAs is not well understood, but it requires the participation of eucaryotic initiation factors eIF-4A, eIF-4B, and eIF-4F and the hydrolysis of ATP. Evidence has accumulated in support of a model in which these initiation factors function to unwind the 5'-proximal secondary structure in mRNA to facilitate ribosome binding. To obtain direct evidence for initiation factor-mediated RNA unwinding, we developed a simple assay to determine RNA helicase activity, and we show that eIF-4A or eIF-4F, in combination with eIF-4B, exhibits helicase activity. A striking and unprecedented feature of this activity is that it functions in a bidirectional manner. Thus, unwinding can occur either in the 5'-to-3' or 3'-to-5' direction. Unwinding in the 5'-to-3' direction by eIF-4F (the cap-binding protein complex), in conjunction with eIF-4B, was stimulated by the presence of the RNA 5' cap structure, whereas unwinding in the 3'-to-5' direction was completely cap independent. These results are discussed with respect to cap-dependent versus cap-independent mechanisms of ribosome binding to eucaryotic mRNAs.

scholarly journals Large G3BP-induced granules trigger eIF2α phosphorylation

2012 ◽  
Vol 23 (18) ◽  
pp. 3499-3510 ◽  
Author(s):  
Lucas C. Reineke ◽  
Jon D. Dougherty ◽  
Philippe Pierre ◽  
Richard E. Lloyd
Keyword(s):  
Stress Granules ◽  
Stress Granule ◽  
Initiation Factor ◽  
Protein Kinase R ◽  
Translational Machinery ◽  
Initiation Factors ◽  
Eif2α Phosphorylation ◽  
Translation Initiation Factors ◽  
Messenger Ribonucleoprotein ◽  
Translation Apparatus

Stress granules are large messenger ribonucleoprotein (mRNP) aggregates composed of translation initiation factors and mRNAs that appear when the cell encounters various stressors. Current dogma indicates that stress granules function as inert storage depots for translationally silenced mRNPs until the cell signals for renewed translation and stress granule disassembly. We used RasGAP SH3-binding protein (G3BP) overexpression to induce stress granules and study their assembly process and signaling to the translation apparatus. We found that assembly of large G3BP-induced stress granules, but not small granules, precedes phosphorylation of eIF2α. Using mouse embryonic fibroblasts depleted for individual eukaryotic initiation factor 2α (eIF2α) kinases, we identified protein kinase R as the principal kinase that mediates eIF2α phosphorylation by large G3BP-induced granules. These data indicate that increasing stress granule size is associated with a threshold or switch that must be triggered in order for eIF2α phosphorylation and subsequent translational repression to occur. Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response.

scholarly journals Uncoupling Stress Granule Assembly and Translation Initiation Inhibition

2009 ◽  
Vol 20 (11) ◽  
pp. 2673-2683 ◽  
Author(s):  
Sophie Mokas ◽  
John R. Mills ◽  
Cristina Garreau ◽  
Marie-Josée Fournier ◽  
Francis Robert ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Binding Protein ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Ribosomal Subunits ◽  
Initiation Factors ◽  
Eif2α Phosphorylation ◽  
Translation Initiation Factors ◽  
Dependent Pathway ◽  
Regulatory Sites

Cytoplasmic stress granules (SGs) are specialized regulatory sites of mRNA translation that form under different stress conditions known to inhibit translation initiation. The formation of SG occurs via two pathways; the eukaryotic initiation factor (eIF) 2α phosphorylation-dependent pathway mediated by stress and the eIF2α phosphorylation-independent pathway mediated by inactivation of the translation initiation factors eIF4A and eIF4G. In this study, we investigated the effects of targeting different translation initiation factors and steps in SG formation in HeLa cells. By depleting eIF2α, we demonstrate that reduced levels of the eIF2.GTP.Met-tRNAiMet ternary translation initiation complexes is sufficient to induce SGs. Likewise, reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. In contrast, depletion of the cap-binding protein eIF4E or preventing its assembly into eIF4F results in modest SG formation. Intriguingly, interfering with the last step of translation initiation by blocking the recruitment of 60S ribosome either with 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamideis or through depletion of the large ribosomal subunits protein L28 does not induce SG assembly. Our study identifies translation initiation steps and factors involved in SG formation as well as those that can be targeted without induction of SGs.

scholarly journals Resistance to Plum pox virus Strain C in Arabidopsis thaliana and Chenopodium foetidum Involves Genome-Linked Viral Protein and Other Viral Determinants and Might Depend on Compatibility With Host Translation Initiation Factors

2014 ◽  
Vol 27 (11) ◽  
pp. 1291-1301 ◽  
Author(s):  
María Calvo ◽  
Sandra Martínez-Turiño ◽  
Juan Antonio García
Keyword(s):  
Arabidopsis Thaliana ◽  
Translation Initiation ◽  
Viral Protein ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Plum Pox Virus ◽  
Initiation Factors ◽  
Translation Initiation Factors

Research performed on model herbaceous hosts has been useful to unravel the molecular mechanisms that control viral infections. The most common Plum pox virus (PPV) strains are able to infect Nicotiana species as well as Chenopodium and Arabidopsis species. However, isolates belonging to strain C (PPV-C) that have been adapted to Nicotiana spp. are not infectious either in Chenopodium foetidum or in Arabidopsis thaliana. In order to determine the mechanism underlying this interesting host-specific behavior, we have constructed chimerical clones derived from Nicotiana-adapted PPV isolates from the D and C strains, which differ in their capacity to infect A. thaliana and C. foetidum. With this approach, we have identified the nuclear inclusion a protein (VPg+Pro) as the major pathogenicity determinant that conditions resistance in the presence of additional secondary determinants, different for each host. Genome-linked viral protein (VPg) mutations similar to those involved in the breakdown of eIF4E-mediated resistance to other potyviruses allow some PPV chimeras to infect A. thaliana. These results point to defective interactions between a translation initiation factor and the viral VPg as the most probable cause of host-specific incompatibility, in which other viral factors also participate, and suggest that complex interactions between multiple viral proteins and translation initiation factors not only define resistance to potyviruses in particular varieties of susceptible hosts but also contribute to establish nonhost resistance.

scholarly journals Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.

1990 ◽  
Vol 10 (3) ◽  
pp. 1134-1144 ◽  
Author(s):  
F Rozen ◽  
I Edery ◽  
K Meerovitch ◽  
T E Dever ◽  
W C Merrick ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Direct Evidence ◽  
Rna Helicase ◽  
Initiation Factor ◽  
Helicase Activity ◽  
Ribosome Binding ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Hydrolysis Of

The mechanism of ribosome binding to eucaryotic mRNAs is not well understood, but it requires the participation of eucaryotic initiation factors eIF-4A, eIF-4B, and eIF-4F and the hydrolysis of ATP. Evidence has accumulated in support of a model in which these initiation factors function to unwind the 5'-proximal secondary structure in mRNA to facilitate ribosome binding. To obtain direct evidence for initiation factor-mediated RNA unwinding, we developed a simple assay to determine RNA helicase activity, and we show that eIF-4A or eIF-4F, in combination with eIF-4B, exhibits helicase activity. A striking and unprecedented feature of this activity is that it functions in a bidirectional manner. Thus, unwinding can occur either in the 5'-to-3' or 3'-to-5' direction. Unwinding in the 5'-to-3' direction by eIF-4F (the cap-binding protein complex), in conjunction with eIF-4B, was stimulated by the presence of the RNA 5' cap structure, whereas unwinding in the 3'-to-5' direction was completely cap independent. These results are discussed with respect to cap-dependent versus cap-independent mechanisms of ribosome binding to eucaryotic mRNAs.

scholarly journals The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7

2019 ◽  
Vol 20 (7) ◽  
pp. 1580 ◽  
Author(s):  
Sunrui Chen ◽  
Cui Feng ◽  
Yan Fang ◽  
Xinying Zhou ◽  
Lei Xu ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Negative Regulator ◽  
Initiation Factor ◽  
Loss Of Function ◽  
Rotavirus Infection ◽  
Eukaryotic Translation ◽  
Initiation Factors ◽  
Eif4f Complex ◽  
Translation Initiation Factors

The eIF4F complex is a translation initiation factor that closely regulates translation in response to a multitude of environmental conditions including viral infection. How translation initiation factors regulate rotavirus infection remains poorly understood. In this study, the knockdown of the components of the eIF4F complex using shRNA and CRISPR/Cas9 were performed, respectively. We have demonstrated that loss-of-function of the three components of eIF4F, including eIF4A, eIF4E and eIF4G, remarkably promotes the levels of rotavirus genomic RNA and viral protein VP4. Consistently, knockdown of the negative regulator of eIF4F and programmed cell death protein 4 (PDCD4) inhibits the expression of viral mRNA and the VP4 protein. Mechanically, we confirmed that the silence of the eIF4F complex suppressed the protein level of IRF1 and IRF7 that exert potent antiviral effects against rotavirus infection. Thus, these results demonstrate that the eIF4F complex is an essential host factor restricting rotavirus replication, revealing new targets for the development of new antiviral strategies against rotavirus infection.

scholarly journals Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity

2021 ◽  
Vol 118 (6) ◽  
pp. e2021719118 ◽  
Author(s):  
Aravinth Kumar Jayabalan ◽  
Srivathsan Adivarahan ◽  
Aakash Koppula ◽  
Rachy Abraham ◽  
Mona Batish ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Early Stage ◽  
Nonstructural Protein ◽  
Granule Formation ◽  
Adp Ribosylation ◽  
Initiation Factors ◽  
Translation Initiation Factors

While biomolecular condensates have emerged as an important biological phenomenon, mechanisms regulating their composition and the ways that viruses hijack these mechanisms remain unclear. The mosquito-borne alphaviruses cause a range of diseases from rashes and arthritis to encephalitis, and no licensed drugs are available for treatment or vaccines for prevention. The alphavirus virulence factor nonstructural protein 3 (nsP3) suppresses the formation of stress granules (SGs)—a class of cytoplasmic condensates enriched with translation initiation factors and formed during the early stage of infection. nsP3 has a conserved N-terminal macrodomain that hydrolyzes ADP-ribose from ADP-ribosylated proteins and a C-terminal hypervariable domain that binds the essential SG component G3BP1. Here, we show that macrodomain hydrolase activity reduces the ADP-ribosylation of G3BP1, disassembles virus-induced SGs, and suppresses SG formation. Expression of nsP3 results in the formation of a distinct class of condensates that lack translation initiation factors but contain G3BP1 and other SG-associated RNA-binding proteins. Expression of ADP-ribosylhydrolase–deficient nsP3 results in condensates that retain translation initiation factors as well as RNA-binding proteins, similar to SGs. Therefore, our data reveal that ADP-ribosylation controls the composition of biomolecular condensates, specifically the localization of translation initiation factors, during alphavirus infection.

scholarly journals Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors

2016 ◽  
Author(s):  
Edward Emmott ◽  
Frederic Sorgeloos ◽  
Sarah L. Caddy ◽  
Surender Vashist ◽  
Stanislav Sosnovtsev ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Host Response ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Innate Response ◽  
Viral Protease ◽  
Viral Protein Synthesis ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Covalently Linked

SummaryNoroviruses produce viral RNAs lacking a 5’ cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. Using a novel mass spectrometry approach we demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex. The suppression of host ISG translation correlates with the activity of the viral protease (NS6) and the activation of cellular caspases leading to the establishment of an apoptotic environment. These results indicate that noroviruses exploit the differences between viral VPg-dependent and cellular cap-dependent translation in order to diminish the host response to infection.

scholarly journals Dendritic BC1 RNA in translational control mechanisms

2005 ◽  
Vol 171 (5) ◽  
pp. 811-821 ◽  
Author(s):  
Huidong Wang ◽  
Anna Iacoangeli ◽  
Daisy Lin ◽  
Keith Williams ◽  
Robert B. Denman ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Fragile X ◽  
Initiation Factor ◽  
Control Mechanisms ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Specific Effector

Translational control at the synapse is thought to be a key determinant of neuronal plasticity. How is such control implemented? We report that small untranslated BC1 RNA is a specific effector of translational control both in vitro and in vivo. BC1 RNA, expressed in neurons and germ cells, inhibits a rate-limiting step in the assembly of translation initiation complexes. A translational repression element is contained within the unique 3′ domain of BC1 RNA. Interactions of this domain with eukaryotic initiation factor 4A and poly(A) binding protein mediate repression, indicating that the 3′ BC1 domain targets a functional interaction between these factors. In contrast, interactions of BC1 RNA with the fragile X mental retardation protein could not be documented. Thus, BC1 RNA modulates translation-dependent processes in neurons and germs cells by directly interacting with translation initiation factors.

scholarly journals Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

2006 ◽  
Vol 17 (10) ◽  
pp. 4212-4219 ◽  
Author(s):  
Rachid Mazroui ◽  
Rami Sukarieh ◽  
Marie-Eve Bordeleau ◽  
Randal J. Kaufman ◽  
Peter Northcote ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Potential Role ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Granule Formation ◽  
Initiation Factors ◽  
Eif2α Phosphorylation ◽  
As Stress ◽  
Cell Stress Response

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation.

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