Staufen1 regulates diverse classes of mammalian transcripts
- 17 May 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 26 (11), 2670-2681
- https://doi.org/10.1038/sj.emboj.7601712
Abstract
It is currently unknown how extensively the double‐stranded RNA‐binding protein Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression. To date, Stau1 binding to the 3′‐untranslated region (3′‐UTR) of ADP ribosylation factor (ARF)1 mRNA has been shown to target ARF1 mRNA for Stau1‐mediated mRNA decay (SMD). ARF1 SMD depends on translation and recruitment of the nonsense‐mediated mRNA decay factor Upf1 to the ARF1 3′‐UTR by Stau1. Here, we demonstrate that Stau1 binds to a complex structure within the ARF1 3′‐UTR. We also use microarrays to show that 1.1 and 1.0% of the 11 569 HeLa‐cell transcripts that were analyzed are upregulated and downregulated, respectively, at least two‐fold upon Stau1 depletion in three independently performed experiments. We localize the Stau1 binding site to the 3′‐UTR of four mRNAs that we define as natural SMD targets. Additionally, we provide evidence that the efficiency of SMD increases during the differentiation of C2C12 myoblasts to myotubes. We propose that Stau1 influences the expression of a wide variety of physiologic transcripts and metabolic pathways.Keywords
This publication has 37 references indexed in Scilit:
- RNA aptamers binding the double-stranded RNA-binding domainRNA, 2006
- hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA DecayMolecular and Cellular Biology, 2006
- CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cellsNature Structural & Molecular Biology, 2005
- Messenger RNA Surveillance: Neutralizing Natural NonsenseCurrent Biology, 2005
- FAST Is a Survival Protein That Senses Mitochondrial Stress and Modulates TIA-1-Regulated Changes in Protein ExpressionMolecular and Cellular Biology, 2004
- The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complexGenes & Development, 2004
- Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamicsNature Reviews Molecular Cell Biology, 2004
- HuR and mRNA stabilityCellular and Molecular Life Sciences, 2001
- Themes in RNA-protein recognitionJournal of Molecular Biology, 1999
- The importance of internal loops within RNA substrates of ADAR1Journal of Molecular Biology, 1999