Abstract
Messenger RNA turnover directed by A + U-rich elements (AREs) involves selected ARE-binding proteins. Whereas several signaling systems may modulate ARE-directed mRNA decay and/or post-translationally modify specific trans-acting factors, it is unclear how these mechanisms are linked. In THP-1 monocytic leukemia cells, phorbol ester-induced stabilization of some mRNAs containing AREs was accompanied by dephosphorylation of Ser83 and Ser87 of polysome-associated p40AUF1. Here, we report that phosphorylation of p40AUF1 influences its ARE-binding affinity as well as the RNA conformational dynamics and global structure of the p40AUF1-ARE ribonucleoprotein complex. Most notably, association of unphosphorylated p40AUF1 induces a condensed RNA conformation upon ARE substrates. By contrast, phosphorylation of p40AUF1 at Ser83 and Ser87 inhibits this RNA structural transition. These data indicate that selective AUF1 phosphorylation may regulate ARE-directed mRNA turnover by remodeling local RNA structures, thus potentially altering the presentation of RNA and/or protein determinants involved in subsequent trans-factor recruitment.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Anisotropy
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dimerization
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Fluorescence Resonance Energy Transfer
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Heterogeneous Nuclear Ribonucleoprotein D0
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Heterogeneous-Nuclear Ribonucleoprotein D / chemistry*
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Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
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Histidine / chemistry
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Humans
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Kinetics
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Models, Chemical
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Models, Statistical
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Molecular Sequence Data
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Nucleic Acid Conformation
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Oligonucleotides / chemistry
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Phosphorylation
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Protein Binding
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Protein Conformation
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Protein Processing, Post-Translational
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Protein Structure, Tertiary
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RNA / metabolism
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RNA, Messenger / metabolism
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Recombinant Proteins / chemistry
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Ribonucleoproteins / chemistry*
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Serine / chemistry
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Signal Transduction
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Spectrometry, Fluorescence
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Thermodynamics
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Time Factors
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Tumor Cells, Cultured
Substances
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HNRNPD protein, human
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Heterogeneous Nuclear Ribonucleoprotein D0
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Heterogeneous-Nuclear Ribonucleoprotein D
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Oligonucleotides
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RNA, Messenger
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Recombinant Proteins
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Ribonucleoproteins
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Serine
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Histidine
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RNA
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Glycogen Synthase Kinase 3 beta
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Cyclic AMP-Dependent Protein Kinases
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Glycogen Synthase Kinase 3