ArticleMolecular cell2025
Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Decoding RNA-protein interactions using high-throughput methods.RNA biology · 2026Review
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Decoding the secrets of life with single-molecular translatomics: A revolutionary strategy in biology.Innovation (Cambridge (Mass.)) · 2026Article
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Investigation of TRMT61B methyltransferase activity on mRNA and its effects on translation.Nucleic acids research · 2026Article
- 5'untranslated regions provide a versatile toolkit for tunable exogenous protein expression.Molecular biology of the cell · 2026Article
- NNature · 2026Article
- m6A-Modified Nucleotide Bases Improve Translation of In Vitro-Transcribed Chimeric Antigen Receptor (CAR) mRNA in T Cells.International journal of molecular sciences · 2026Article
- Investigation of TRMT61B methyltransferase activity on mRNA and its effects on translation.bioRxiv : the preprint server for biology · 2025Article
- Overcoming the eIF2α Brake in Human Cell-Derived Translation Systems.bioRxiv : the preprint server for biology · 2025Article
- mRNA-based immunotherapy platform targeting endometrial cancer.Journal of translational medicine · 2025Article
- HydraRNA: a hybrid architecture based full-length RNA language model.Genome biology · 2025Article
- Comparative CRISPRi screens reveal a human stem cell dependence on mRNA translation-coupled quality control.Nature structural & molecular biology · 2025Article
- A foundation language model to decipher diverse regulation of RNAs.Genome biology · 2025Article
- Protocol for monitoring mRNA translation and degradation in human cell-free lysates.STAR protocols · 2025Article
- Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail,Molecular therapy. Nucleic acids · 2025Article
- Uncovering mRNA sequences that control translation initiation.Nature reviews. Molecular cell biology · 2025Article
- A generative language model decodes contextual constraints on codon choice for mRNA design.bioRxiv : the preprint server for biology · 2025Article
- Selective Translation Under Heat Shock: Integrating HSP70 mRNA Regulation with Cellular Stress Responses in Yeast and Mammals.Molecular biology of the cell · 2025Review
- Decoding post-transcriptional gene expression controls in trypanosomatids using machine learning.Wellcome open research · 2025Article
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9 authors.
Funding
Abstract
mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs. Using systems-level biochemistry, we quantify ribosome recruitment to tens of thousands of human 5' untranslated regions (UTRs) including alternative isoforms and identify sequences that mediate 200-fold effects. We observe widespread effects of coding sequences on translation initiation and identify small regulatory elements of 3-6 nucleotides that are sufficient to potently affect translational output. Incorporation of N1-methylpseudouridine (m1Ψ) selectively enhances translation by specific 5' UTRs that we demonstrate surpass those of current mRNA vaccines. Our approach is broadly applicable to dissecting mechanisms of human translation initiation and engineering more potent therapeutic mRNAs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.