AU-rich elements and associated factors: are there unifying principles?

Barreau, Carine; Paillard, Luc; Osborne, Howard Beverley

doi:10.1093/nar/gki1012

Cited by 894 publications

(1,038 citation statements)

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“…The rapid deadenylation of unstable mRNAs, such as those encoding mammalian cytokines or proto-oncogenes, is mediated by AREs (AU-rich elements), which have been divided into three classes, depending on the presence and the distribution of the core motif AUUUA (Chen and Shyu, 1995). A number of ARE-binding proteins have been characterized, and a role, either stimulatory or inhibitory, in mRNA deadenylation has been established for some of them (reviewed in Barreau et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Oligomerization of EDEN‐BP is required for specific mRNA deadenylation and binding

Cosson

Gautier-Courteille

Maniey

et al. 2006

Biology of the Cell

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Background information. mRNA deadenylation [shortening of the poly(A) tail] is often triggered by specific sequence elements present within mRNA 3 untranslated regions and generally causes rapid degradation of the mRNA. In vertebrates, many of these deadenylation elements are called AREs (AU-rich elements). The EDEN (embryo deadenylation element) sequence is a Xenopus class III ARE. EDEN acts by binding a specific factor, EDEN-BP (EDEN-binding protein), which in turn stimulates deadenylation.Results. We show here that EDEN-BP is able to oligomerize. A 27-amino-acid region of EDEN-BP was identified as a key domain for oligomerization. A mutant of EDEN-BP lacking this region was unable to oligomerize, and a peptide corresponding to this region competitively inhibited the oligomerization of full-length EDEN-BP. Impairing oligomerization by either of these two methods specifically abolished EDEN-dependent deadenylation. Furthermore, impairing oligomerization inhibited the binding of EDEN-BP to its target RNA, demonstrating a strong coupling between EDEN-BP oligomerization and RNA binding.Conclusions. These data, showing that the oligomerization of EDEN-BP is required for binding of the protein on its target RNA and for EDEN-dependent deadenylation in Xenopus embryos, will be important for the identification of cofactors required for the deadenylation process.

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Section: Introductionmentioning

confidence: 99%

Oligomerization of EDEN‐BP is required for specific mRNA deadenylation and binding

Cosson

Gautier-Courteille

Maniey

et al. 2006

Biology of the Cell

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“…the zinc finger binding protein, tristetraprolin (TTP), and K homology splicing-regulatory protein (KSRP)). For reviews on RNA binding proteins, see references [20][21][22]. There has not been any details about the identities of RNA binding proteins that bind type-I IFN mRNAs, but, a 65 kDa protein was identified to bind to a 28 nucleotide AU-rich element in the IFN-β 3′UTR and it is inducible by polyI-polyC [23].…”

Section: Post-transcriptional Regulation Of Ifn-beta: the "Super-indumentioning

confidence: 99%

Post-transcriptional control of the interferon system

Khabar

Young

2007

Biochimie

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The interferon (IFN) system is a well-controlled network of signaling, transcriptional, and posttranscriptional processes that orchestrate host defense against microbes. The IFN response comprises a multi-array of IFN-stimulated gene products that mediate a variety of biological processes designed to control infection and regulate specific immune responses. In this review, we focus on posttranscriptional mechanisms of gene regulation that occur during the course of IFN induction and during the response of cells to IFN. Post-transcriptional mechanisms involve different levels of regulation such as mRNA stability, alternative splicing, and translation. Such controls offer a fine tuning mechanism for efficient and rapid response and as a negative feedback control in IFN biosynthesis and response.

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“…These processes allow cells to rapidly adjust the expression pattern of regulatory factors and respond transiently to internal and external signals, including cell proliferation, signal transduction, inflammatory stimuli and radiation. A well-known important cis-acting sequence element that controls stability of diseaseimplicated mRNAs is the AU-rich element (ARE) found in the 3 untranslated region (3 UTR) of many, but not all, unstable mRNAs of various growth factors, cytokines, proto-oncogenes and transcription factors (Barreau et al, 2006). The first identified ARE sequence motif was the pentamer AUUUA .…”

Section: Introductionmentioning

confidence: 99%

“…Class II AREs contain at least two overlapping UUAUUUA(U/A)(U/A) nonamers. Class III AREs are less well defined and do not contain an AUUUA pentamer (Barreau et al, 2006;.…”

Section: Introductionmentioning

confidence: 99%

“…The core sequence, which has been used in mammalian reporter systems (Xu et al, 1997) and in the yeast S. cerevisiae (Vasudevan and Peltz, 2001), is used in this study and is also underlined suggest that the surrounding context or secondary structure is important for recognition of the ARE of MFA2 by regulatory factors (Duttagupta et al, 2003). Stem-loop structures downstream (Barreau et al, 2006) or within an ARE (Chabanon et al, 2005;Fialcowitz et al, 2005) have already been identified and shown to be important for ARE regulation.…”

Section: Introductionmentioning

confidence: 99%

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The human c‐fos and TNFα AU‐rich elements show different effects on mRNA abundance and protein expression depending on the reporter in the yeast Pichia pastoris

Lautz

Ståhl

Lang

2009

Yeast

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AU-rich elements (AREs) are located in the 3 untranslated region (3 UTR) of their host genes and tightly regulate mRNA degradation and expression. Examples for this kind of regulation are the human proto-oncogene c-fos and the cytokine TNFα. Despite large effort in this field, the exact mechanism of ARE-mediated mRNA turnover remains unclear. In this work we analysed the effects of c-fos-and TNFα AREs on mRNA abundance and protein expression of selected human cDNAs in the yeast Pichia pastoris. This yeast is exceedingly well known for its excellent protein production capacity; however, ARE-like mechanisms have not been studied in this yeast to date. Interestingly, we observed both stabilizing and destabilizing effects of the c-fos ARE, whereas the TNFα ARE has a destabilizing or expression-reducing function in all tested cDNAs. Based on this observation, we introduced a number of single-point mutations upstream of the introduced c-fos ARE into the 3 UTR of a single cDNA in order to demonstrate the importance of ARE-flanking sequences for their own regulation. In conclusion, we illustrate that the analysis of ARE-mediated effects on mRNA abundance and protein expression of a reporter depends on the sequence of the reporter itself as well as the ARE-surrounding sequences within the 3 UTR. For this reason, we question whether already established reporter constructs in other cellular systems display the true type of regulation of the tested AREs for its original host gene. Finally, we propose that AREs should be analysed in their native sequence context.

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AU-rich elements and associated factors: are there unifying principles?

Cited by 894 publications

References 185 publications

Oligomerization of EDEN‐BP is required for specific mRNA deadenylation and binding

Oligomerization of EDEN‐BP is required for specific mRNA deadenylation and binding

Post-transcriptional control of the interferon system

The human c‐fos and TNFα AU‐rich elements show different effects on mRNA abundance and protein expression depending on the reporter in the yeast Pichia pastoris

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