ArticleRNA biology2020
Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes.
Article in RNA biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 20 citations in OpenAlex.
- Reduced UPF1 levels in senescence impair nonsense-mediated mRNA decay.Communications biology · 2025Article
- Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model.Cell genomics · 2024Article
- Modulation of prion protein expression through cryptic splice site manipulation.bioRxiv : the preprint server for biology · 2023Article
- Translational buffering by ribosome stalling in upstream open reading frames.PLoS genetics · 2022Article
- Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough.The Journal of clinical investigation · 2022Article
- NMD inhibition by 5-azacytidine augments presentation of immunogenic frameshift-derived neoepitopes.iScience · 2021Article
- Effect of small molecule eRF3 degraders on premature termination codon readthrough.Nucleic acids research · 2021Article
- Disrupting upstream translation in mRNAs is associated with human disease.Nature communications · 2021Article
- Nonsense-Mediated RNA Decay Factor UPF1 Is Critical for Posttranscriptional and Translational Gene Regulation in Arabidopsis.The Plant cell · 2020Article
- CTELS: A Cell-Free System for the Analysis of Translation Termination Rate.Biomolecules · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to its role in translation termination, eRF3A has been implicated in the nonsense-mediated mRNA decay (NMD) pathway through its interaction with UPF1. NMD is a RNA quality control mechanism, which detects and degrades aberrant mRNAs as well as some normal transcripts including those that harbour upstream open reading frames in their 5' leader sequence. In this study, we used RNA-sequencing and ribosome profiling to perform a genome wide analysis of the effect of either eRF3A or UPF1 depletion in human cells. Our bioinformatics analyses allow to delineate the features of the transcripts controlled by eRF3A and UPF1 and to compare the effect of each of these factors on gene expression. We find that eRF3A and UPF1 have very different impacts on the human transcriptome, less than 250 transcripts being targeted by both factors. We show that eRF3A depletion globally derepresses the expression of mRNAs containing translated uORFs while UPF1 knockdown derepresses only the mRNAs harbouring uORFs with an AUG codon in an optimal context for translation initiation. Finally, we also find that eRF3A and UPF1 have opposite effects on ribosome protein gene expression. Together, our results provide important elements for understanding the impact of translation termination and NMD on the human transcriptome and reveal novel determinants of ribosome biogenesis regulation.
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