Argonaute protein binding Met-tRNAiMet represses translation initiation
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ABSTRACT:
PROVIDER: PRJNA750397 | ENA |
REPOSITORIES: ENA
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Project description:Initiation factor 2 (eIF2) delivering the initiator methionine transfer RNA (Met-tRNAiMet) to the ribosome is a conserved key step in translation initiation. Argonaute (Ago) proteins were initially identified as eukaryotic translation initiation factor 2C,2 (EIF2C2). In the past 2 decades, Argonaute were extensively studied as a core component of RNA induced gene silencing, although various model raised the exact mechanism of Ago in translation repression remains elusive. Here we found Ago protein directly bind Met- tRNAiMet independent of miRNA binding, which interfere the formation of the ternary complex eIF2–GTP–Met- tRNAiMet. Ago proteins can solely inhibit protein synthesis via competing tRNAiMet with eIF2. Our findings elucidate a physical link between Ago and tRNAiMet and provide mechanistic insight into translation repression by Ago proteins.
2022-02-01 | GSE181004 | GEO
Project description:In yeast and mammals, activated GCN2 can phosphorylate its substrate eIF2α, which is a part of the eIF2-GTP-Met-tRNAiMet ternary complex. The eIF2α phosphorylation blocks the ternary complex formation and therefore inhibits translation initiation. Meanwhile, GCN2 activation associates with ribosomes and some translation elongation factors such as eEF1A. In Neurospora crassa, the homolog of GCN2 is CPC-3. Ribosome profiling and accompanying RNA-seq experiments in this project were used to explore the effects of CPC-3 on translation kinetics. Here we show that poor codon usage of mRNAs with long CDS preferentially causes CPC-3 activation, which in turn suppresses the translation initiation and elongation in both codon usage and CDS length dependent manner.
2021-08-10 | GSE168595 | GEO
Project description:c-Met induces tumor initiation and stemness in HCC cells through the regulation of CD44s via AKT signaling. Over-expression of CD44s in c-Met and CD44s negative cells induce both a stemness and mesenchymal phenotype independent of c-Met. The down regulation of CD44s or c-Met was compared to Scrambled control to investigate the effects of CD44s or c-Met on global changes of mesenchymal or stemness markers.
2012-05-30 | E-GEOD-38343 | biostudies-arrayexpress
Project description:c-Met induces tumor initiation and stemness in HCC cells through the regulation of CD44s via AKT signaling. Over-expression of CD44s in c-Met and CD44s negative cells induce both a stemness and mesenchymal phenotype independent of c-Met.
2012-05-31 | GSE38343 | GEO
Project description:Synonymous codon usage regulates translation initiation
| PRJNA837608 | ENA
Project description:The 43S pre-initiation complex (PIC) assembly requires establishment of numerous interactions among eukaryotic initiation factors (eIFs), Met-tRNAiMet and the small ribosomal subunit (40S). Owing to several differences in the structure and composition of kinetoplastidian 40S compared to their mammalian counterparts, translation initiation in trypanosomatids is suspected to display substantial variability. Here, we determined the structure of the 43S PIC from Trypanosoma cruzi, the Chagas disease parasite, showing numerous specific features, such as different eIF3 structure and interactions with the large rRNA expansion segments 9S, 7S and 6S, and the association of a kinetoplastid-specific ~245 kDa DDX60-like helicase. We also revealed a previously undetermined binding site of the eIF5 C-terminal domain, and terminal tails of eIF2β, eIF1, eIF1A and eIF3 c and d subunits, uncovering molecular details of their critical activities.
2020-03-25 | PXD016063 | Pride
Project description:We studied the initiation signals located in the translational initiation region (TIR) and identified the role for recognition of the initiation signals in each individual stage during formation of the initiation complexes. Sequencing the randomized mRNA libraries captured by translation initiation complexes
2016-07-27 | E-GEOD-69782 | biostudies-arrayexpress
Project description:Translation initiation landscape of tomato-infecting virus
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Project description:Ribo-seq with firefly luciferase optimality reporters to determine whether incomplete translation and/or inhibited translation initiation is responsible for the reduced ribosome occupancy on nonoptimal transcripts.
2022-05-16 | GSE202900 | GEO
Project description:The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context. Previous findings suggest that the factor eIF1 discriminates against non-AUG start codons by impeding full accommodation of Met-tRNAi in the P site of the 40S ribosomal subunit, necessitating eIF1 dissociation for start codon selection. Consistent with this, yeast eIF1 substitutions that weaken its binding to the PIC increase initiation at UUG codons on a mutant his4 mRNA and particular synthetic mRNA reporters; and also at the AUG start codon of the mRNA for eIF1 itself owing to its poor Kozak context. It was not known however whether such eIF1 mutants increase initiation at suboptimal start codons genome-wide. By ribosome profiling, we show that the eIF1-L96P variant confers increased translation of numerous upstream open reading frames (uORFs) initiating with either near-cognate codons (NCCs) or AUGs in poor context. The increased uORF translation is frequently associated with reduced translation of the downstream main coding sequences (CDS). Initiation is also elevated at the NCCs initiating N-terminal extensions on GRS1 and ALA1 mRNAs, and at a small set of main CDS AUG codons with especially poor context, including that of eIF1 itself. Thus, eIF1 acts throughout the yeast translatome to discriminate against NCC start codons and AUGs in poor context; and impairing this function enhances the repressive effects of uORFs on CDS translation and alters the ratios of protein isoforms translated from near-cognate versus AUG start codons.
2019-10-18 | GSE138599 | GEO