scholarly journals A helicase-independent activity of eIF4A in promoting mRNA recruitment to the human ribosome

2017 ◽  
Vol 114 (24) ◽  
pp. 6304-6309 ◽  
Author(s):  
Masaaki Sokabe ◽  
Christopher S. Fraser
Keyword(s):  
Translation Initiation ◽  
Messenger Rna ◽  
Initiation Factor ◽  
Helicase Activity ◽  
Initiation Factors ◽  
A Subunit ◽  
And Migration ◽  
Atp Binding And Hydrolysis ◽  
A Site ◽  
Full Reduction

In the scanning model of translation initiation, the decoding site and latch of the 40S subunit must open to allow the recruitment and migration of messenger RNA (mRNA); however, the precise molecular details for how initiation factors regulate mRNA accommodation into the decoding site have not yet been elucidated. Eukaryotic initiation factor (eIF) 3j is a subunit of eIF3 that binds to the mRNA entry channel and A-site of the 40S subunit. Previous studies have shown that a reduced affinity of eIF3j for the 43S preinitiation complex (PIC) occurs on eIF4F-dependent mRNA recruitment. Because eIF3j and mRNA bind anticooperatively to the 43S PIC, reduced eIF3j affinity likely reflects a state of full accommodation of mRNA into the decoding site. Here, we have used a fluorescence-based anisotropy assay to quantitatively determine how initiation components coordinate their activities to reduce the affinity of eIF3j during the recruitment of mRNA to the 43S PIC. Unexpectedly, we show that a full reduction in eIF3j affinity for the 43S PIC requires an ATP-dependent, but unwinding-independent, activity of eIF4A. This result suggests that in addition to its helicase activity, eIF4A uses the free energy of ATP binding and hydrolysis as a regulatory switch to control the conformation of the 43S PIC during mRNA recruitment. Therefore, our results define eIF4A as a universal initiation factor in cap-dependent translation initiation that functions beyond its role in RNA unwinding.

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 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 OseIF3h Regulates Plant Growth and Pollen Development at Translational Level Presumably through Interaction with OsMTA2

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1101
Author(s):  
Yuqing Huang ◽  
Peng Zheng ◽  
Xuejiao Liu ◽  
Hao Chen ◽  
Jumin Tu
Keyword(s):  
Plant Growth ◽  
Translation Initiation ◽  
Pollen Development ◽  
Messenger Rna ◽  
Protein Biosynthesis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Sequencing Data ◽  
Knock Out ◽  
Translational Level

The initiation stage of protein biosynthesis is a sophisticated process tightly regulated by numerous initiation factors and their associated components. However, the mechanism underlying translation initiation has not been completely understood in rice. Here, we showed knock-out mutation of the rice eukaryotic translation initiation factor 3 subunit h (OseIF3h) resulted in plant growth retardation and seed-setting rate reduction as compared to the wild type. Further investigation demonstrated an interaction between OseIF3h and OsMTA2 (mRNA adenosine methylase 2), a rice homolog of METTL3 (methyltransferase-like 3) in mammals, which provided new insight into how N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is engaged in the translation initiation process in monocot species. Moreover, the RIP-seq (RNA immunoprecipitation sequencing) data suggested that OseIF3h was involved in multiple biological processes, including photosynthesis, cellular metabolic process, precursor metabolites, and energy generation. Therefore, we infer that OseIF3h interacts with OsMTA2 to target a particular subset of genes at translational level, regulating plant growth and pollen development.

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.

Epidermal induction and inhibition of neural fate by translation initiation factor 4AIII

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4235-4242
Author(s):  
D.C. Weinstein ◽  
E. Honore ◽  
A. Hemmati-Brivanlou
Keyword(s):  
Cell Fate ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Bmp Signaling ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Neural Fate ◽  
Morphogenetic Protein ◽  
Dissociated Cells ◽  
A Site

Bone Morphogenetic Protein-4 (BMP-4) is a potent epidermal inducer and inhibitor of neural fate. We have used differential screening to identify genes involved in epidermal induction downstream of BMP-4 and report here evidence of a novel translational mechanism that regulates the division of the vertebrate ectoderm into regions of neural and epidermal fate. In dissociated Xenopus ectoderm, addition of ectopic BMP-4 leads to an increase in the expression of translation initiation factor 4AIII (eIF-4AIII), a divergent member of the eIF-4A gene family until now characterized only in plants. In the gastrula embryo, Xenopus eIF-4AIII (XeIF-4AIII) expression is elevated in the ventral ectoderm, a site of active BMP signal transduction. Moreover, overexpression of XeIF-4AIII induces epidermis in dissociated cells that would otherwise adopt a neural fate, mimicking the effects of BMP-4. Epidermal induction by XeIF-4AIII requires both an active BMP signaling pathway and an extracellular intermediate. Our results suggest that XeIF-4AIII can regulate changes in cell fate through selective mRNA translation. We propose that BMPs and XeIF-4AIII interact through a positive feedback loop in the ventral ectoderm of the vertebrate gastrula.

scholarly journals Crystal structure of the MIF4G domain of the Trypanosoma cruzi translation initiation factor EIF4G5

2019 ◽  
Vol 75 (12) ◽  
pp. 738-743
Author(s):  
Lucca Pietro Camillo dos Santos ◽  
Bruno Moisés de Matos ◽  
Brenda Cecilia de Maman Ribeiro ◽  
Nilson Ivo Tonin Zanchin ◽  
Beatriz Gomes Guimarães
Keyword(s):  
Crystal Structure ◽  
Translation Initiation ◽  
Specific Interaction ◽  
Three Dimensional ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Dimensional Structure ◽  
Initiation Factors ◽  
Genes Encoding ◽  
Rna Complexes

Kinetoplastida, a class of early-diverging eukaryotes that includes pathogenic Trypanosoma and Leishmania species, display key differences in their translation machinery compared with multicellular eukaryotes. One of these differences involves a larger number of genes encoding eIF4E and eIF4G homologs and the interaction pattern between the translation initiation factors. eIF4G is a scaffold protein which interacts with the mRNA cap-binding factor eIF4E, the poly(A)-binding protein, the RNA helicase eIF4A and the eIF3 complex. It contains the so-called middle domain of eIF4G (MIF4G), a multipurpose adaptor involved in different protein–protein and protein–RNA complexes. Here, the crystal structure of the MIF4G domain of T. cruzi EIF4G5 is described at 2.4 Å resolution, which is the first three-dimensional structure of a trypanosomatid MIF4G domain to be reported. Structural comparison with IF4G homologs from other eukaryotes and other MIF4G-containing proteins reveals differences that may account for the specific interaction mechanisms of MIF4G despite its highly conserved overall fold.

scholarly journals The translation initiation factor eIF-4B contains an RNA-binding region that is distinct and independent from its ribonucleoprotein consensus sequence.

1994 ◽  
Vol 14 (4) ◽  
pp. 2307-2316 ◽  
Author(s):  
N Méthot ◽  
A Pause ◽  
J W Hershey ◽  
N Sonenberg
Keyword(s):  
Translation Initiation ◽  
Rna Binding ◽  
Consensus Sequence ◽  
Point Mutations ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Rna Recognition Motif ◽  
Helicase Activity ◽  
Binding Region ◽  
Stimulation Of

eIF-4B is a eukaryotic translation initiation factor that is required for the binding of ribosomes to mRNAs and the stimulation of the helicase activity of eIF-4A. It is an RNA-binding protein that contains a ribonucleoprotein consensus sequence (RNP-CS)/RNA recognition motif (RRM). We examined the effects of deletions and point mutations on the ability of eIF-4B to bind a random RNA, to cooperate with eIF-4A in RNA binding, and to enhance the helicase activity of eIF-4A. We report here that the RNP-CS/RRM alone is not sufficient for eIF-4B binding to RNA and that an RNA-binding region, located between amino acids 367 and 423, is the major contributor to RNA binding. Deletions which remove this region abolish the ability of eIF-4B to cooperate with eIF-4A in RNA binding and the ability to stimulate the helicase activity of eIF-4A. Point mutations in the RNP-CS/RRM had no effect on the ability of eIF-4B to cooperate with eIF-4A in RNA binding but significantly reduced the stimulation of eIF-4A helicase activity. Our results indicate that the carboxy-terminal RNA-binding region of eIF-4B is essential for eIF-4B function and is distinct from the RNP-CS/RRM.

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