ArticleRNA (New York, N.Y.)2013
Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways.
Article in RNA (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 141 citations in OpenAlex.
- Beyond quality control: biological roles of nonsense-mediated RNA decay.The EMBO journal · 2026Review
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- The function of mRNA quality control in aging and age-related diseases.The Journal of biological chemistry · 2026Review
- Rare heterozygous de novo variants in RAPGEF2 are associated with a neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- Dynamic RNA binding and unfolding by nonsense-mediated mRNA decay factor UPF2.RNA (New York, N.Y.) · 2025Article
- Endonucleolytic cleavage is the primary mechanism of decay elicited byGenome research · 2025Article
- Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications.Molecular biotechnology · 2025Review
- Article
- Nonsense-Mediated mRNA Decay: Mechanistic Insights and Physiological Significance.Molecular biotechnology · 2024Review
- Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions.eLife · 2024Article
- A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated mRNA Decay.Genes · 2024Article
- Differences in alternative splicing and their potential underlying factors between animals and plants.Journal of advanced research · 2024Review
- Global impact of unproductive splicing on human gene expression.Nature genetics · 2024Article
- Deep Mutational Scanning in Disease-related Genes with Saturation Mutagenesis-Reinforced Functional Assays (SMuRF).bioRxiv : the preprint server for biology · 2024Article
- Exon-junction complex association with stalled ribosomes and slow translation-independent disassembly.Nature communications · 2024Article
- UPF1 regulates mRNA stability by sensing poorly translated coding sequences.Cell reports · 2024Article
- A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.Nucleic acids research · 2024Article
- Nonsense-mediated mRNA decay, a simplified view of a complex mechanism.BMB reports · 2023Review
- Global impact of aberrant splicing on human gene expression levels.bioRxiv : the preprint server for biology · 2023Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nonsense-mediated mRNA decay (NMD) is a eukaryotic post-transcriptional gene regulation mechanism that eliminates mRNAs with the termination codon (TC) located in an unfavorable environment for efficient translation termination. The best-studied NMD-targeted mRNAs contain premature termination codons (PTCs); however, NMD regulates even many physiological mRNAs. An exon-junction complex (EJC) located downstream from a TC acts as an NMD-enhancing signal, but is not generally required for NMD. Here, we compared these "EJC-enhanced" and "EJC-independent" modes of NMD with regard to their requirement for seven known NMD factors in human cells using two well-characterized NMD reporter genes (immunoglobulin μ and β-Globin) with or without an intron downstream from the PTC. We show that both NMD modes depend on UPF1 and SMG1, but detected transcript-specific differences with respect to the requirement for UPF2 and UPF3b, consistent with previously reported UPF2- and UPF3-independent branches of NMD. In addition and contrary to expectation, a higher sensitivity of EJC-independent NMD to reduced UPF2 and UPF3b concentrations was observed. Our data further revealed a redundancy of the endo- and exonucleolytic mRNA degradation pathways in both modes of NMD. Moreover, the relative contributions of both decay pathways differed between the reporters, with PTC-containing immunoglobulin μ transcripts being preferentially subjected to SMG6-mediated endonucleolytic cleavage, whereas β-Globin transcripts were predominantly degraded by the SMG5/SMG7-dependent pathway. Overall, the surprising heterogeneity observed with only two NMD reporter pairs suggests the existence of several mechanistically distinct branches of NMD in human cells.
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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.