ArticleScientific reports2020
Translation elongation factor 2 depletion by siRNA in mouse liver leads to mTOR-independent translational upregulation of ribosomal protein genes.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- STRIP2 promotes hepatocellular carcinoma progression and immune evasion: a potential prognostic biomarker and therapeutic target.Journal of gastrointestinal oncology · 2025Article
- Detecting ribosome collisions with differential rRNA fragment analysis in ribosome profiling data.NAR genomics and bioinformatics · 2025Article
- A generative framework for enhanced cell-type specificity in rationally designed mRNAs.bioRxiv : the preprint server for biology · 2024Article
- Article
- Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues.Pharmaceutics · 2024Article
- Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.PloS one · 2024Article
- The alphavirus nonstructural protein 2 NTPase induces a host translational shut-off through phosphorylation of eEF2 via cAMP-PKA-eEF2K signaling.PLoS pathogens · 2023Article
- Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8Nature communications · 2022Article
- eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior.EMBO reports · 2022Article
- Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes.Journal of the Royal Society, Interface · 2022Article
- Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein.RNA (New York, N.Y.) · 2021Article
- Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein.bioRxiv : the preprint server for biology · 2021Article
- Upregulation of 5'-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor.Scientific reports · 2020Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Due to breakthroughs in RNAi and genome editing methods in the past decade, it is now easier than ever to study fine details of protein synthesis in animal models. However, most of our understanding of translation comes from unicellular organisms and cultured mammalian cells. In this study, we demonstrate the feasibility of perturbing protein synthesis in a mouse liver by targeting translation elongation factor 2 (eEF2) with RNAi. We were able to achieve over 90% knockdown efficacy and maintain it for 2 weeks effectively slowing down the rate of translation elongation. As the total protein yield declined, both proteomics and ribosome profiling assays showed robust translational upregulation of ribosomal proteins relative to other proteins. Although all these genes bear the TOP regulatory motif, the branch of the mTOR pathway responsible for translation regulation was not activated. Paradoxically, coordinated translational upregulation of ribosomal proteins only occurred in the liver but not in murine cell culture. Thus, the upregulation of ribosomal transcripts likely occurred via passive mTOR-independent mechanisms. Impaired elongation sequesters ribosomes on mRNA and creates a shortage of free ribosomes. This leads to preferential translation of transcripts with high initiation rates such as ribosomal proteins. Furthermore, severe eEF2 shortage reduces the negative impact of positively charged amino acids frequent in ribosomal proteins on ribosome progression.
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