Publications by authors named "Ana Tamarkin-Ben-Harush"
Article Synopsis
- During translation initiation, eIF4G1 interacts with eIF4E and eIF1, but the specific functions of eIF4G1 and eIF1 together are not well understood.
- Researchers identified inhibitors i14G1-10 and i14G1-12 that bind to eIF4G1, blocking translation both in lab settings and within cells, with their effectiveness varying based on eIF4G1 levels.
- These inhibitors also mimic the effects of eIF1 and eIF4G1 on start codon selection, activate stress-response genes during ER stress, and present a new mechanism for understanding translation under stress, suggesting potential applications in treating diseases linked to translation issues.
Translation initiation of most mRNAs involves m7G-cap binding, ribosomal scanning, and AUG selection. Initiation from an m7G-cap-proximal AUG can be bypassed resulting in leaky scanning, except for mRNAs bearing the ranslation nitiator of hort 5' ntranslated region (TISU) element. m7G-cap binding is mediated by the eukaryotic initiation factor 4E (eIF4E)-eIF4G1 complex.
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- Canonical translation initiation usually involves the ribosome scanning the mRNA, but short 5' untranslated regions (5'UTR) can be translated without this scanning process.
- These short 5'UTRs often contain a key 12-nucleotide element called TISU, which aids in this type of translation by interacting with ribosomal proteins and influencing translational strength.
- Research shows that TISU's efficiency is enhanced by eukaryotic initiation factor 1A (eIF1A), indicating a complex relationship between TISU, ribosomal proteins, and the translation initiation process.
Article Synopsis
- - The study investigates how transcription start-site (TSS) selection and alternative promoter (AP) usage affect gene expression and translation under energy stress conditions.
- - It was found that the binding affinity of eIF4E to capped-RNAs varies with the type of initiating nucleotide and particularly decreases with 5'cytidine during stress, leading to significant changes in translation.
- - The research also reveals that stress triggers an increase in differentially translated APs, leading to the production of modified isoforms of translation regulators eIF4A and Pabp, which play unique roles during the translational stress response.
Article Synopsis
- * In cells lacking AMPKα1/AMPKα2, some translation inhibition remains, suggesting alternative mechanisms are at play.
- * The study highlights a unique translation initiation process using TISU, which allows specific mitochondrial mRNAs to persist in translation under energy stress, emphasizing the role of eIF1 and eIF4F in this mechanism.
Background: Variability in protein levels is generated through intricate control of the different gene decoding phases. Presently little is known about the links between the various gene expression stages. Here we investigated the relationship between transcription and translation regulatory properties encoded in mammalian genes.
View Article and Find Full Text PDFMicroRNAs are transcribed by RNA polymerase II but the transcriptional features influencing their synthesis are poorly defined. Here we report that a TATA box in microRNA and protein-coding genes is associated with increased sensitivity to slow RNA polymerase II. Promoters driven by TATA box or NF-κB elicit high re-initiation rates, but paradoxically lower microRNA levels.
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