Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of stress on the binding affinity of yeast eIF4F components to their target RNAs

ABSTRACT: Translation factors eIF4E and eIF4G form eIF4F, which binds to mRNAs to promote ribosome recruitment and translation initiation. We were interested in analysing the effects of stresses on eIF4F interactions with individual mRNAs. We used a RIP-seq approach to assess how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change in response to three stresses: 1) addition of hydrogen peroxide; 2) amino acids withdrawal; and, 3) glucose withdrawal. We find that acute stress leads to changes in eIF4FmRNA interactions that are shared among each factor and across the stresses imposed.

INSTRUMENT(S): AB SOLiD 4 System

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: David Talavera

PROVIDER: E-MTAB-5836 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis- multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/ Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex. This study concentrated on a particular cancer model and studied the role of eIF4E and eIF4GI in the design of the cells' proteome. We used an unbiased, high throughput system to evaluate the individual importance of eIF4E and eIF4GI levels in MM. We used models of eIF4E or eIF4GI knocked down (KD) MM cell line RPMI 8226 and profiled their respective translated transcription factors (TF), often tumor suppressors or oncogenes. Furthermore, we assessed the KDs' microRNAs repertoires and cells' phenotype. Significant differences were observed between eIF4E and eIF4GI knockdown imprints.

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Effect of stress on the binding affinity of yeast eIF4F components to their target RNAs

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