Correlation between intrinsic mRNA stability and the affinity of AUF1 (hnRNP D) and HuR for A+U-rich mRNAs.
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 comparison ofAUF1 and HuR binding properties has been made. Therefore, we examined the relative affinities of p37AUF1 and HuR for a diverse set ofARE-containing mRNAs encoding beta-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 stability of chimeric beta-globin mRNA constructs. Although the relative affinity ofAUF1 and HuR are generally predictive of mRNA stability, we find that certain mRNA sequences do not conform to these generalizations.
Blaxall
Burns C
BC
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Pende
Aldo
A
Wu
Steven C
SC
Port
J David
JD
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000225:Adenine; D000818:Animals; D000954:Antigens, Surface; D001482:Base Composition; D001483:Base Sequence; D006224:Cricetinae; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D024202:Electrophoretic Mobility Shift Assay; D005914:Globins / Q000235:genetics*; D006207:Half-Life; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays; D014498:Uracil
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D014498:Uracil; D005914:Globins; D000225:Adenine