Cited by 656RNA Research and SplicingRNA and protein synthesis mechanismsRNA Interference and Gene Delivery

AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2

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Vasudevan, Shobha, Steitz, Joan A.·2007·Cell

Abstract

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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Crossref · 10.1016/j.cell.2007.01.038

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  • In serum starved cells, AGO2 and FXR1 were associated with AU-rich elements at the 3' UTR to activate translation.

    “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).”

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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)
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
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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