ArticleRNA (New York, N.Y.)2023
Translation reinitiation after uORFs does not fully protect mRNAs from nonsense-mediated decay.
Article in RNA (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- A microprotein atlas of the human frontal cortex in Alzheimer's disease.Nature aging · 2026Article
- Uncovering the isoform-resolution kinetic landscape of nonsense-mediated mRNA decay with EZbakR.Genome biology · 2026Article
- Evaluating the reliability of tools for mRNA annotation and IRES studies.bioRxiv : the preprint server for biology · 2026Article
- A homozygous synonymous variant in SMG5, encoding a nonsense-mediated mRNA decay factor, causes developmental delay with growth retardation and relative macrocephaly.Human genetics · 2026Article
- Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to Pumilio-mediated decay.Nucleic acids research · 2026Article
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.Genome medicine · 2025Article
- Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to RNA-binding protein-directed decay.bioRxiv : the preprint server for biology · 2025Article
- Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals.Genome biology · 2025Article
- Full-length mRNA sequencing resolves novel variation in 5' UTR length for genes expressed during human CD4 T-cell activation.Immunogenetics · 2025Article
- ShortStop: a machine learning framework for microprotein discovery.BMC methods · 2025Article
- Tiny but mighty: Diverse functions of uORFs that regulate gene expression.Computational and structural biotechnology journal · 2024Review
- Current limitations in predicting mRNA translation with deep learning models.Genome biology · 2024Article
- Ribosome Pausing Negatively Regulates Protein Translation in Maize Seedlings during Dark-to-Light Transitions.International journal of molecular sciences · 2024Article
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.Nucleic acids research · 2023Article
- Principles, mechanisms, and biological implications of translation termination-reinitiation.RNA (New York, N.Y.) · 2023Article
- The Emerging Role of uORF-Encoded uPeptides and HLA uLigands in Cellular and Tumor Biology.Cancers · 2022Review
- Features and factors that dictate if terminating ribosomes cause or counteract nonsense-mediated mRNA decay.The Journal of biological chemistry · 2022Review
- 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
5 authors at 1 institution in 1 country.
Funding
Abstract
It is estimated that nearly 50% of mammalian transcripts contain at least one upstream open reading frame (uORF), which are typically one to two orders of magnitude smaller than the downstream main ORF. Most uORFs are thought to be inhibitory as they sequester the scanning ribosome, but in some cases allow for translation reinitiation. However, termination in the 5' UTR at the end of uORFs resembles premature termination that is normally sensed by the nonsense-mediated mRNA decay (NMD) pathway. Translation reinitiation has been proposed as a method for mRNAs to prevent NMD. Here, we test how uORF length influences translation reinitiation and mRNA stability in HeLa cells. Using custom 5' UTRs and uORF sequences, we show that reinitiation can occur on heterologous mRNA sequences, favors small uORFs, and is supported when initiation occurs with more initiation factors. After determining reporter mRNA half-lives in HeLa cells and mining available mRNA half-life data sets for cumulative predicted uORF length, we conclude that translation reinitiation after uORFs is not a robust method for mRNAs to prevent NMD. Together, these data suggest that the decision of whether NMD ensues after translating uORFs occurs before reinitiation in mammalian cells.
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Registered trials
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.