ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
UU/UA dinucleotide frequency reduction in coding regions results in increased mRNA stability and protein expression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
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- Compare Analysis of Codon Usage Bias of Nuclear Genome in Eight Sapindaceae Species.International journal of molecular sciences · 2024Article
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- Phylogenetics Study to Compare Chloroplast Genomes in Four Magnoliaceae Species.Current issues in molecular biology · 2023Article
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- mRNA Vaccine Platform: mRNA Production and Delivery.Russian journal of bioorganic chemistry · 2023Article
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- mRNA vaccines: A novel weapon to control infectious diseases.Frontiers in microbiology · 2022Review
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- Post-transcriptional screen of cancer amplified genes identifies ERBB2/Her2 signaling as AU-rich mRNA stability-promoting pathway.Oncogenesis · 2021Article
- An Update on mRNA-Based Viral Vaccines.Vaccines · 2021Review
- ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6.The EMBO journal · 2021Article
- Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein.Molecular brain · 2021Article
- The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester"Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
UU and UA dinucleotides are rare in mammalian genes and may offer natural selection against endoribonuclease-mediated mRNA decay. This study hypothesized that reducing UU and UA (UW) dinucleotides in the mRNA-coding sequence, including the codons and the dicodon boundaries, may promote resistance to mRNA decay, thereby increasing protein production. Indeed, protein expression from UW-reduced coding regions of enhanced green fluorescent protein (EGFP), luciferase, interferon-α, and hepatitis B surface antigen (HBsAg) was higher when compared to the wild-type protein expression. The steady-state level of UW-reduced EGFP mRNA was higher and the mRNA half-life was also longer. Ectopic expression of the endoribonuclease, RNase L, did not reduce the wild type or UW-reduced mRNA. A mutant form of the mRNA decay-promoting protein, tristetraprolin (TTP/ZFP36), which has a point mutation in the zinc-finger domain (C124R), was used. The wild-type EGFP mRNA but not the UW-reduced mRNA responded to the dominant negative action of the C124R ZFP36/TTP mutant. The results indicate the efficacy of the described rational approach to formulate a general scheme for boosting recombinant protein production in mammalian cells.
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