ArticleNature communications2022
A nascent peptide code for translational control of mRNA stability in human cells.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Beyond codon optimality: codon pairs regulate mRNA stability dependent on translation.bioRxiv : the preprint server for biology · 2026Article
- Nascent chain folding status modulates ribosome dynamics and mRNA stability through the ribosome-associated chaperone Zuo1.Molecular cell · 2026Article
- Article
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Circadian clock control of ribosome composition promotes rhythmic translation and termination fidelity.Cell reports · 2025Article
- Barcoded CRISPR screens reveal RNA regulatory networks.Nature methods · 2025Article
- The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus.Nature reviews. Genetics · 2025Review
- Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.PLoS biology · 2024Article
- tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation iniScience · 2024Article
- AntigenBoost: enhanced mRNA-based antigen expression through rational amino acid substitution.Briefings in bioinformatics · 2024Article
- Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells.bioRxiv : the preprint server for biology · 2024Article
- Massively parallel identification of sequence motifs triggering ribosome-associated mRNA quality control.Nucleic acids research · 2024Article
- Integrated multiplexed assays of variant effect reveal determinants of catechol-O-methyltransferase gene expression.Molecular systems biology · 2024Article
- Translation-dependent and -independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T cell activation.Genome research · 2024Article
- Codon-optimization in gene therapy: promises, prospects and challenges.Frontiers in bioengineering and biotechnology · 2024Review
- From cancer therapy to cardiac safety: the role of proteostasis in drug-induced cardiotoxicity.Frontiers in pharmacology · 2024Review
- Quantification of elongation stalls and impact on gene expression in yeast.RNA (New York, N.Y.) · 2023Article
- Control of mRNA fate by its encoded nascent polypeptide.Molecular cell · 2023Review
- Quantification of elongation stalls and impact on gene expression in yeast.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
3 authors.
Funding
Abstract
Stability of eukaryotic mRNAs is associated with their codon, amino acid, and GC content. Yet, coding sequence motifs that predictably alter mRNA stability in human cells remain poorly defined. Here, we develop a massively parallel assay to measure mRNA effects of thousands of synthetic and endogenous coding sequence motifs in human cells. We identify several families of simple dipeptide repeats whose translation triggers mRNA destabilization. Rather than individual amino acids, specific combinations of bulky and positively charged amino acids are critical for the destabilizing effects of dipeptide repeats. Remarkably, dipeptide sequences that form extended β strands in silico and in vitro slowdown ribosomes and reduce mRNA levels in vivo. The resulting nascent peptide code underlies the mRNA effects of hundreds of endogenous peptide sequences in the human proteome. Our work suggests an intrinsic role for the ribosome as a selectivity filter against the synthesis of bulky and aggregation-prone peptides.
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