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

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AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2

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

DOI 10.1016/j.cell.2007.01.038PMC PMC3430382

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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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Authors: Vasudevan, S., & Steitz, J. A.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Steitz, Joan A.
ORCID: Vasudevan, Shobha
Steitz, Joan A.
Venue: Cell
Publisher: Elsevier BV
Published: 2007-03
Volume: 128
Issue: 6
Pages: 1105-1118
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2007.01.038
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2366 d)
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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AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2

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