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AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2
Open accessAbstract
AU-rich elements (AREs), present in mRNA 3'-UTRs, are potent posttranscriptional regulatory signals that can rapidly effect changes in mRNA stability and translation, thereby dramatically altering gene expression with clinical and developmental consequences. In human cell lines, the TNFalpha ARE enhances translation relative to mRNA levels upon serum starvation, which induces cell-cycle arrest. An in vivo crosslinking-coupled affinity purification method was developed to isolate ARE-associated complexes from activated versus basal translation conditions. We surprisingly found two microRNP-related proteins, fragile-X-mental-retardation-related protein 1 (FXR1) and Argonaute 2 (AGO2), that associate with the ARE exclusively during translation activation. Through tethering and shRNA-knockdown experiments, we provide direct evidence for the translation activation function of both FXR1 and AGO2 and demonstrate their interdependence for upregulation. This novel cell-growth-dependent translation activation role for FXR1 and AGO2 allows new insights into ARE-mediated signaling and connects two important posttranscriptional regulatory systems in an unexpected way.
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“In serum starved cells, AGO2 and another protein related to the miRNA-protein complex (microRNPs), Fragile-x-mental retardation related protein 1 (FXR1), were associated with AU-rich elements (AREs) at 3′ UTR to activate translation (55).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [55]
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Metadata
- Authors
- Vasudevan, S., & Steitz, J. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Steitz, Joan A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 128
- Issue
- 6
- Pages
- 1105-1118
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3430382
- OpenAlex
- W2010763857
- Cited by
- 656
- References
- 66
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 25 · 2023: 25 · 2022: 31 · 2021: 38 · 2020: 31 · 2019: 26 · 2018: 21 · 2017: 13 · 2016: 39 · 2015: 32 · 2014: 34 · 2013: 48 · 2012: 43
- FWCI
- 21.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM26154, R01GM026154)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AU-rich elements, FXR1, Argonaute 2, translation activation, post-transcriptional regulation, mRNA 3' UTR, microRNA-induced silencing complex, TNF-α, serum deprivation, cell cycle arrest, protein-protein interaction, cell growth
- MeSH terms
- Cell Cycle, Cell Line, Chromatography, Affinity, Humans, Monocytes, Peptide Initiation Factors, Polyribosomes, Ribonucleoproteins, Protein Biosynthesis, Tumor Necrosis Factor-alpha, Eukaryotic Initiation Factor-2, Up-Regulation, RNA-Binding Proteins, Culture Media, Serum-Free, Genes, Reporter, 3' Untranslated Regions, Regulatory Sequences, Ribonucleic Acid, Serum, Luciferases, Firefly, Argonaute Proteins
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