Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. (affbiotech.com)
MRNAs6
RNA-immunoprecipitation sequencing (RIP-Seq) of the two eIF4A paralogs revealed that eIF4A1 preferentially binds to mRNAs containing terminal oligopyrimidine (TOP) motifs, whose translation is rapidly repressed upon mTOR inhibition. (biorxiv.org)
Ribosome profiling revealed that the deletion of EIF4A1 , but not EIF4A2 , rendered the translation of TOP mRNAs resistant to mTOR inactivation. (biorxiv.org)
Moreover, eIF4A1 enhances the affinity between TOP mRNAs and LARP1 and thus ensures stronger translation repression upon mTORC1 inhibition. (biorxiv.org)
The mechanisms involved in the stress-induced translation have been investigated for a small number of key transcription factors (for example, yeast general control nondepressible 4 (GCN4) 12 and mammalian activating transcription factor 4 (ATF4) 13 ), whose translation is normally inhibited by the uORFs in the 5' leader sequences of their mRNAs. (biorxiv.org)
Moreover, recent global ribosome-sequencing (Ribo-seq, sequencing of ribosome-protected RNA fragments) studies have shown that uORFs are a prevalent feature in eukaryotic mRNAs, not limited to these few well-studied examples 19 - 21 . (biorxiv.org)
eIF4E binds to the 7 methyl GTP cap structure of eukaryotic mRNAs. (affbiotech.com)
Helicase1
In vitro, wild type recombinant eIF4A1 and its phospho-null variant both support translation in cell free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and was also deficient in ATP hydrolysis and helicase activity. (aber.ac.uk)
EIF4E1
Eukaryotic translation initiation factor 4 gamma has been shown to interact with MKNK1, EIF4A1, EIF4E, MKNK2 and PABPC1. (wikipedia.org)
Mammalian2
Two mammalian eIF4A paralogs, eIF4A1 and eIF4A2, have been assumed to be redundant because of their high homology, and the difference in their functions has been poorly understood. (biorxiv.org)
Previously, we found that eukaryotic initiation factor (eIF) 4A interacts with cyclin dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. (aber.ac.uk)
Phosphorylation1
Upon stress, phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) decreases the available ternary complex, resulting in reduced translation initiation from the start codons of uORFs (uAUGs) and prolonged scanning of the preinitiation complex to translate the downstream main open reading frames (mORFs) to promote cell survival 12 - 15 . (biorxiv.org)
Translational1
Here, we show that eIF4A1, but not eIF4A2, enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. (biorxiv.org)
Arabidopsis1
In vivo, a phospho-null (APGR) variant of the Arabidopsis eIF4A1 protein retains the ability to functionally complement a mutant (eif4a1) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. (aber.ac.uk)
Protein synthesis1
Our data show that the distinct protein interactions of these highly homologous translation factor paralogs shape protein synthesis during mTORC1 inhibition and provide a unique example of the repressive role of a universal translation activator. (biorxiv.org)
Therefore, immunohistochemical analysis was performed on over 3000 breast tumors to investigate the relationship among expression of eIF4A1, the helicase-modulating proteins eIF4B, eIF4E and PDCD4, and clinical outcome. (nature.com)
We found eIF4A1, eIF4B and eIF4E to be independent predictors of poor outcome in ER-negative disease, while in contrast, the eIF4A1 inhibitor PDCD4 was related to improved outcome in ER-positive breast cancer. (nature.com)
Eukaryotic translation initiation factor 4 gamma has been shown to interact with MKNK1, EIF4A1, EIF4E, MKNK2 and PABPC1. (wikipedia.org)
eIF4A forms an eIF4F complex together with the 7-methylguanosine (m 7 G) cap-binding factor eIF4E and scaffold protein eIF4G. (biorxiv.org)
There is mounting evidence that dysregulation of mRNA translation supports the survival and adaptation of cancer cells, which has stimulated clinical interest in targeting elements of the translation machinery and, in particular, components of the eukaryotic initiation factor 4F (eIF4F) complex such as eIF4E. (bvsalud.org)
EIF4G1
May excert its function by hindering the interaction between EIF4A1 and EIF4G. (nih.gov)
Binds2
RNA-immunoprecipitation sequencing (RIP-Seq) of the two eIF4A paralogs revealed that eIF4A1 preferentially binds to mRNAs containing terminal oligopyrimidine (TOP) motifs, whose translation is rapidly repressed upon mTOR inhibition. (biorxiv.org)
This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. (nih.gov)
EIF4A5
One of the most abundant is eIF4A, which is required during the initiation phase of protein synthesis to unwind regions of highly structured mRNA that would otherwise impede the scanning ribosome. (nature.com)
Two mammalian eIF4A paralogs, eIF4A1 and eIF4A2, have been assumed to be redundant because of their high homology, and the difference in their functions has been poorly understood. (biorxiv.org)
Among the eIFs, the most abundant factor is eIF4A, a DEAD-box RNA-binding protein. (biorxiv.org)
Mammalian cells possess two highly homologous cytoplasmic eIF4A paralogs, eIF4A1 and eIF4A2, that are 90% identical in amino acid sequence ( Nielsen and Trachsel, 1988 ). (biorxiv.org)
In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. (nih.gov)
Eukaryotic cells harness a number of eukaryotic translation initiation factors (eIFs) to achieve accurate and efficient initiation ( Sonenberg and Hinnebusch, 2009 ). (biorxiv.org)
Ribosome profiling revealed that the deletion of EIF4A1 , but not EIF4A2 , rendered the translation of TOP mRNAs resistant to mTOR inactivation. (biorxiv.org)
BACKGROUND: Eukaryotic initiation factor (eIF) 4G plays an important role in assembling the initiation complex required for ribosome binding to mRNA and promote translation. (bvsalud.org)
EIF4A21
7 The isoform eIF4A2 can also participate in translation initiation, but is also implicated in the function of microRNAs. (nature.com)
Proteins3
Alterations in the expression of several eIF4A1 activity-modulating proteins have been observed in many cancers. (nature.com)
In particular, several proteins of the translation initiation complex were identified as bona fide CMA substrates in multiple cancer cell lines of distinct origin and we show that CMA suppresses cellular translation. (nih.gov)
In 2000, the zinc finger factor snail (Snail Homologue 1), hereinafter referred to as SNAI1, is a transcriptional suppressor that seems to control protein stability, nuclear localization and function by phosphorylation and zinc transport proteins. (biomedcentral.com)
Pathway1
17. Astragaloside IV exhibits anti-tumor function in gastric cancer via targeting circRNA dihydrolipoamide S-succinyltransferase (circDLST)/miR-489-3p/ eukaryotic translation initiation factor 4A1(EIF4A1) pathway. (nih.gov)
EIF4F2
Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. (bvsalud.org)
Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. (bvsalud.org)
Inhibits1
Inhibits translation initiation and cap-dependent translation. (nih.gov)
Consistent with these data, modulation of eIF4A1, eIF4B and PCDC4 expression in cultured MCF7 cells all restricted breast cancer cell growth and cycling. (nature.com)
Expression of eIF4A1 itself has not been widely investigated in tumors. (nature.com)
Finally, high expression of translation initiation-related genes and PHBs genes correlated with poor survival and unfavorable clinical parameters in patients with CLL. (bvsalud.org)
Gene1
Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the EIF4G1 gene. (wikipedia.org)
Complex1
Here, we rather show that PHBs are directly associated with the eukaryotic initiation factor (eIF)4F translation complex and are targeted by FL3. (bvsalud.org)
Data1
However, the above findings and data from a number of model systems implicate eIF4A1 in the malignant phenotype. (nature.com)
Eukaryotic translation initiation factor (eIF) 4A - a DEAD-box RNA-binding protein - plays an essential role in translation initiation. (biorxiv.org)
We also unraveled a new and direct role of PHBs in translation initiation, thus creating new therapeutic opportunities for patients with CLL. (bvsalud.org)