ArticleNucleic acids research2022
Global 5'-UTR RNA structure regulates translation of a SERPINA1 mRNA.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Identification of PTPRR gene associated with cirrhosis and sarcopenia based on bioinformatics and machine learning.European journal of clinical nutrition · 2026Article
- Domain arrangement-driven immunogenicity of a computationally designed mRNA vaccine targeting PPE68, IrtA, and PE9 of Mycobacterium tuberculosis.Scientific reports · 2026Article
- A New Class of Pathogenic Non-Coding Variants in GLA.International journal of molecular sciences · 2026Article
- Protein Fragments: From Biomarkers to Therapeutic Targets-A Focus on α1-Antitrypsin-Derived Peptides.Mediators of inflammation · 2026Review
- Precursor RNA structural patterns at SF3B1 mutation sensitive cryptic 3' splice sites.RNA biology · 2025Article
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Study of Stress Granule Core Protein AtUBP1b PhosphorylationPlants (Basel, Switzerland) · 2025Article
- Airway-applied mRNA vaccine needs tailored sequence design and high standard purification that removes devastating dsRNA contaminant.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Altered polyadenylation site usage in SERPINA1 3'UTR in response to cellular stress affects A1AT protein expression.Scientific reports · 2025Article
- Structural Features of 5' Untranslated Region in Translational Control of Eukaryotes.International journal of molecular sciences · 2025Review
- Protein binding in an mRNA 5'-UTR sterically hinders translation.RNA (New York, N.Y.) · 2025Article
- Shared genetic architecture of non-viral cirrhosis with several pleiotropic traits: A nested case-control study in the UK Biobank.Liver international communications · 2024Article
- Testing Alpha-1 Antitrypsin Deficiency in Black Populations.Advances in respiratory medicine · 2023Review
- Impact of the Diversity in the 5' UTR on Translation Regulation.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
SERPINA1 mRNAs encode the protease inhibitor α-1-antitrypsin and are regulated through post-transcriptional mechanisms. α-1-antitrypsin deficiency leads to chronic obstructive pulmonary disease (COPD) and liver cirrhosis, and specific variants in the 5'-untranslated region (5'-UTR) are associated with COPD. The NM_000295.4 transcript is well expressed and translated in lung and blood and features an extended 5'-UTR that does not contain a competing upstream open reading frame (uORF). We show that the 5'-UTR of NM_000295.4 folds into a well-defined multi-helix structural domain. We systematically destabilized mRNA structure across the NM_000295.4 5'-UTR, and measured changes in (SHAPE quantified) RNA structure and cap-dependent translation relative to a native-sequence reporter. Surprisingly, despite destabilizing local RNA structure, most mutations either had no effect on or decreased translation. Most structure-destabilizing mutations retained native, global 5'-UTR structure. However, those mutations that disrupted the helix that anchors the 5'-UTR domain yielded three groups of non-native structures. Two of these non-native structure groups refolded to create a stable helix near the translation initiation site that decreases translation. Thus, in contrast to the conventional model that RNA structure in 5'-UTRs primarily inhibits translation, complex folding of the NM_000295.4 5'-UTR creates a translation-optimized message by promoting accessibility at the translation initiation site.
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Registered trials
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