ArticleProceedings of the National Academy of Sciences of the United States of America2019
mRNA structure regulates protein expression through changes in functional half-life.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 349 papers, 2 of them syntheses that pooled it.
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Who cites it
349 citing papers in PubMed, 2 syntheses or guidelines pooled it.
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- The impact of psuedouridine modification on human tRNA.Biochemical Society transactions · 2026Review
- Fine-scale structural information substantially improves mRNA therapeutic stability prediction.Molecular therapy. Nucleic acids · 2026Article
- A protocol for computational design of mRNA vaccines with high functionality and specificity.Biology direct · 2026Article
- Intermittency and Predictability of a Cafeteria Diet Shape Food Intake, Adiposity, and Neurobehavioral Outcomes in Rats.Nutrients · 2026Article
- Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
289 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Messenger RNAs (mRNAs) encode information in both their primary sequence and their higher order structure. The independent contributions of factors like codon usage and secondary structure to regulating protein expression are difficult to establish as they are often highly correlated in endogenous sequences. Here, we used 2 approaches, global inclusion of modified nucleotides and rational sequence design of exogenously delivered constructs, to understand the role of mRNA secondary structure independent from codon usage. Unexpectedly, highly expressed mRNAs contained a highly structured coding sequence (CDS). Modified nucleotides that stabilize mRNA secondary structure enabled high expression across a wide variety of primary sequences. Using a set of eGFP mRNAs with independently altered codon usage and CDS structure, we find that the structure of the CDS regulates protein expression through changes in functional mRNA half-life (i.e., mRNA being actively translated). This work highlights an underappreciated role of mRNA secondary structure in the regulation of mRNA stability.
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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 OpenQuestion graph.