Mammalian Hsp70 and Hsp110 Proteins Bind to RNA Motifs Involved in mRNA Stability

Henics, Tamás; Nagy, Eszter; Oh, Hyun Ju; Csermely, Péter; Gabain, Alexander von; Subjeck, John R.

doi:10.1074/jbc.274.24.17318

Cited by 121 publications

(114 citation statements)

References 42 publications

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“…This free HSP70 protein is then able to affect further HSP70 production by attenuating transcription or accelerating the degradation of its own mRNA. Prior studies have shown that binding of HSP70 to a target polypeptide causes a conformational change in the protein, reducing its RNA binding capacity (Henics et al 1999). The binding of HSP70, directly or indirectly, to its own message during recovery after stress may be related to the decay process.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the presence of ATP disrupted HSP70 binding to the Hsp70 transcript. Several lymphokine and protooncogene mRNAs contain destabilizing AU-rich 3Ј-untranslated regions, which have been shown to interact with HSP70 in in vitro conditions (Henics et al 1999;Zimmer et al 2001). Indeed, deletion of the 3Ј-untranslated regions of Drosophila Hsp70 mRNA resulted in stabilization of the message (Simcox et al 1985;Petersen et al 1989).…”

Section: Discussionmentioning

confidence: 99%

“…RNA was then extracted using an acid/guanidinium thiocyanate/phenol/chloroform protocol (Chomczynski and Sacchi 1987). Mobility shift assays were carried out as previously described (Henics et al 1999), with the following modifications: 1 g of recombinant Hsp70 protein (StressGen) was used, reactions were incubated for 30 min at 30ЊC, 7.5 U of RNase T1 were used alone, and samples were analyzed by 5% nondenaturing polyacrylamide gel electrophoresis (PAGE) in Tris-borate-EDTA (TBE) buffer (0.09 tris-borate pH 8.0, 0.002 EDTA) and the signal was detected using a PhosphorImager.…”

Section: In Vitro Rna Transcription and Electrophoretic Mobility Shifmentioning

confidence: 99%

“…When protein synthesis resumes, a threshold HSP70 level is needed to destabilize these mRNAs (DiDomenico et al 1982). HSP70 has been shown in vitro to bind AU-rich sequences, particularly AUUUA, in the 3Ј-untranslated region of lymphokine mRNAs; these sequences are common to many unstable mRNAs and may alter message stability (Spicher et al 1998;Henics et al 1999;Malter 2001). Finally, the Hsp70 mRNA itself contains a class III AU-rich element that lacks a defined AU-containing repeated sequence but has a generally AU-rich 3Ј-untranslated region (Malter 2001).…”

Section: Introductionmentioning

confidence: 99%

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Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Balakrishnan¹,

Maio²

2006

Cell Stress Chaper

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Expression of heat shock proteins is a cellular response to a variety of stressors. HSP70, the major stressinduced heat shock protein, is involved in repair and protection after the insult. However, the prolonged presence of this protein is detrimental. Consequently, Hsp70 expression must be tightly regulated. We have previously shown an increase in the degradation of Hsp70 messenger ribonucleic acid (mRNA) paralleling the accumulation of HSP70. Incubation of cells with transcriptional and translational inhibitors after heat shock resulted in a significant reduction in Hsp70 mRNA degradation. These observations suggest that newly synthesized, stress-induced factors might be involved in the decay of Hsp70 mRNA. We found that HSP70 binds directly to Hsp70 mRNA, as demonstrated by immunoprecipitation. This observation was confirmed by RNA gel-shift assays. These results are evidence for a novel and likely direct interaction between HSP70 and Hsp70 mRNA in cells after stress. This interaction may be part of a self-limiting mechanism to reduce HSP70 production, thus avoiding potential toxic effects of this protein in the absence of stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Rna Transcription and Electrophoretic Mobility Shifmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Balakrishnan¹,

Maio²

2006

Cell Stress Chaper

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“…Thus, associated trans-acting proteins may modulate the decay kinetics of ARE-containing mRNAs positively or negatively. Additionally, a growing number of AREbinding proteins have been described to which no specific functions have been ascribed (27)(28)(29)(30)(31).…”

mentioning

confidence: 99%

Regulation of A + U-rich Element-directed mRNA Turnover Involving Reversible Phosphorylation of AUF1

Wilson

Sutphen

et al. 2003

Journal of Biological Chemistry

125

114

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Proteins binding A ؉ U-rich elements (AREs) contribute to the rapid cytoplasmic turnover of mRNAs containing these sequences. However, this process is a regulated event and may be accelerated or inhibited by myriad signal transduction systems. For example, monocyte adherence at sites of inflammation or tissue injury is associated with inhibition of ARE-directed mRNA decay, which contributes to rapid increases in cytokine and inflammatory mediator production. Here, we show that acute exposure of THP-1 monocytic leukemia cells to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate mimics several features of monocyte adherence, including rapid induction and stabilization of ARE-containing mRNAs encoding interleukin-1␤ and tumor necrosis factor ␣. Additionally, TPA treatment alters the activity of cytoplasmic complexes that bind AREs, including complexes containing the ARE-specific, mRNA-destabilizing factor, AUF1. Analyses of AUF1 from control and TPA-treated cells indicated that posttranslational modifications of the major cytoplasmic isoform, p40 AUF1 , are altered concomitant with changes in RNA binding activity and stabilization of ARE-containing mRNAs. In particular, p40 AUF1 recovered from polysomes was phosphorylated on Ser 83 and Ser 87 in untreated cells but lost these modifications following TPA treatment. We propose that selected signal transduction pathways may regulate ARE-directed mRNA turnover by reversible phosphorylation of polysome-associated p40 AUF1 .In eukaryotes, cytoplasmic mRNA stability is an important checkpoint in the control of gene expression. Many mRNAs encoding regulatory proteins like cytokines, inflammatory mediators, and oncoproteins are constitutively unstable. This ensures that the steady-state levels of these mRNAs, and hence their potential for translation, remain low but also that new steady-state levels are approached quickly following changes in the rate of mRNA synthesis (reviewed in Ref. 1). In mammals, a common feature of many unstable mRNAs is the presence of an A ϩ U-rich element (ARE) 1 within the 3Ј-untranslated region (3Ј-UTR). These elements range from 40 to 150 nucleotides in length and exhibit significant variability in sequence composition, but they usually include one or more AUUUA motifs within a U-rich context (2). In general, mRNA turnover mediated by AREs consists of rapid 3Ј 3 5Ј shortening of the poly(A) tail, followed by decay of the mRNA body (3, 4).The regulation of mRNA decay kinetics by AREs involves their association with any of a number of cellular ARE-binding factors (reviewed in Ref. 5). One such factor, AUF1 (also referred to as heterogeneous nuclear ribonucleoprotein D), is expressed as a family of four protein isoforms resulting from alternative splicing of a common pre-mRNA (6). The larger isoforms, designated by their apparent molecular weights as p42 AUF1 and p45 AUF1 , are largely nuclear (7), probably due to the presence of a binding determinant for components of the nuclear scaffold (8). By contrast, p37 AUF1 and p40 AUF1 lack this seq...

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Unconventional RNA‐binding proteins: an uncharted zone in RNA biology

Albihlal

Gerber

2018

FEBS Letters

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The RNA-binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-binding proteins that contain characteristic RNA-binding domains, many proteins that lack such domains but have other well-characterized cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved 'unconventional' RNA-binding proteins that act in central carbon metabolism, stress response or regulation of transcription.

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Mammalian Hsp70 and Hsp110 Proteins Bind to RNA Motifs Involved in mRNA Stability

Cited by 121 publications

References 42 publications

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism

Regulation of A + U-rich Element-directed mRNA Turnover Involving Reversible Phosphorylation of AUF1

Unconventional RNA‐binding proteins: an uncharted zone in RNA biology

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