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PMID: 17382880 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Cell ·Vol. 128 ·No. 6 ·2007-03-23 ·Pages 1105-18

Vasudevan S, Steitz JA

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.

MeSH Terms
3' Untranslated Regions/genetics,metabolism Argonaute Proteins Cell Cycle Cell Line Chromatography, Affinity Culture Media, Serum-Free Eukaryotic Initiation Factor-2 Genes, Reporter Humans Luciferases, Firefly/genetics Monocytes/cytology,metabolism Peptide Initiation Factors/metabolism Polyribosomes/metabolism Protein Biosynthesis RNA-Binding Proteins/metabolism Regulatory Sequences, Ribonucleic Acid Ribonucleoproteins/metabolism Serum/metabolism Tumor Necrosis Factor-alpha/genetics Up-Regulation
Chemicals
3' Untranslated Regions AGO2 protein, human Argonaute Proteins Culture Media, Serum-Free Eukaryotic Initiation Factor-2 FXR1 protein, human Peptide Initiation Factors RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid Ribonucleoproteins TNF protein, human Tumor Necrosis Factor-alpha Luciferases, Firefly
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Vasudevan Shobha
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
Steitz Joan A
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.01.038
Published
2007-03-23
Pages
1105-18
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3430382
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026154 · United States
NIGMS NIH HHS · GM26154 · United States
Corrections
CommentIn
PMID: 17382873
External Links
PubMed source DOI: 10.1016/j.cell.2007.01.038 PMC Full Text View journal details
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