Correlation between intrinsic mRNA stability and the affinity of AUF1 (hnRNP D) and HuR for A+U-rich mRNAs

B. C. Blaxall; A. Pende; S. C. Wu; J. D. Port

doi:10.1023/A:1014819016552

Correlation between intrinsic mRNA stability and the affinity of AUF1 (hnRNP D) and HuR for A+U-rich mRNAs

B. C. Blaxall, A. Pende, S. C. Wu, J. D. Port

Integrative Biology and Physiology

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Presence of A+U-rich elements (AREs) within 3′-untranslated regions (3′UTRs) of numerous mRNAs has been associated with rapid mRNA turnover; however, the interaction of specific factors with AREs is also associated with mRNA stabilization. Recently, two ARE binding proteins with putative mRNA destabilizing (AUF1) and stabilizing (HuR) properties have been described. However, no direct comparisons of AUF1 and HuR binding properties has been made. Therefore, we examined the relative affinities of p37AUF1 and HuR for a diverse set of ARE-containing mRNAs encoding β-adrenergic receptors, a proto-oncogene, and a cytokine. We find that high-affinity AUF1 binding appears to require elements beyond primary nucleotide sequence. In contrast, binding of HuR appears considerably less constrained. As a functional correlate, we determined the ability of these specific mRNA sequences to affect the ability of chimeric β-globin mRNA constructs. Although the relative affinity of AUF1 and HuR are generally predictive of mRNA stability, we find that certain mRNA sequences do not conform to these generalizations.

Original language	English (US)
Pages (from-to)	1-11
Number of pages	11
Journal	Molecular and cellular biochemistry
Volume	232
Issue number	1-2
DOIs	https://doi.org/10.1023/A:1014819016552
State	Published - 2002

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant HL51239 (JDP), grant CWGS-46-97 from the Colorado Affiliate of the American Heart Association (JDP), a University of Colorado Cancer Center grant (JDP), a PhRMA Foundation predoctoral fellowship (BCB) and Training Grant GM07635 from the National Institutes of Health. This work was also supported in part by AstraZeneca L.P., Wayne, PA, USA. We would like to thank Dr. Gary Brewer for providing us with the cDNA for His6-p37AUF1, for an anti-AUF1 antibody, and for many helpful discussions. We would also like to thank Dr. Henry Furneaux for providing us with GST-HuR and with an anti-HuR antibody.

Keywords

AUF1
Beta-adrenergic receptor
HuR
hnRNP D
mRNA binding protein
mRNA stability

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title = "Correlation between intrinsic mRNA stability and the affinity of AUF1 (hnRNP D) and HuR for A+U-rich mRNAs",

abstract = "Presence of A+U-rich elements (AREs) within 3′-untranslated regions (3′UTRs) of numerous mRNAs has been associated with rapid mRNA turnover; however, the interaction of specific factors with AREs is also associated with mRNA stabilization. Recently, two ARE binding proteins with putative mRNA destabilizing (AUF1) and stabilizing (HuR) properties have been described. However, no direct comparisons of AUF1 and HuR binding properties has been made. Therefore, we examined the relative affinities of p37AUF1 and HuR for a diverse set of ARE-containing mRNAs encoding β-adrenergic receptors, a proto-oncogene, and a cytokine. We find that high-affinity AUF1 binding appears to require elements beyond primary nucleotide sequence. In contrast, binding of HuR appears considerably less constrained. As a functional correlate, we determined the ability of these specific mRNA sequences to affect the ability of chimeric β-globin mRNA constructs. Although the relative affinity of AUF1 and HuR are generally predictive of mRNA stability, we find that certain mRNA sequences do not conform to these generalizations.",

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author = "Blaxall, {B. C.} and A. Pende and Wu, {S. C.} and Port, {J. D.}",

note = "Funding Information: This work was supported by National Institutes of Health grant HL51239 (JDP), grant CWGS-46-97 from the Colorado Affiliate of the American Heart Association (JDP), a University of Colorado Cancer Center grant (JDP), a PhRMA Foundation predoctoral fellowship (BCB) and Training Grant GM07635 from the National Institutes of Health. This work was also supported in part by AstraZeneca L.P., Wayne, PA, USA. We would like to thank Dr. Gary Brewer for providing us with the cDNA for His6-p37AUF1, for an anti-AUF1 antibody, and for many helpful discussions. We would also like to thank Dr. Henry Furneaux for providing us with GST-HuR and with an anti-HuR antibody.",

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AU - Port, J. D.

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Correlation between intrinsic mRNA stability and the affinity of AUF1 (hnRNP D) and HuR for A+U-rich mRNAs

Abstract

Bibliographical note

Keywords

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