The mammalian RNA-binding protein (RBP) HuR associates with numerous mRNAs encoding proteins with
roles in cell division, cell survival, immune response, and differentiation. HuR was known to stabilize many of these
mRNAs and/or modulated their translation, but the molecular processes by which HuR affected the fate of target mRNAs
was largely unknown. Evidence accumulated over the past five years has revealed that the influence of HuR on many
bound transcripts depends on HuR’s interplay with microRNAs which associate with the same mRNAs. Here, we review
the interactions of HuR and microRNAs – both competitive and cooperative – that govern expression of shared target
mRNAs. Competition between HuR and microRNAs typically results in enhanced gene expression if the HuR-mRNA interaction
prevails, and in repression if the microRNA remains associated. Cooperation between HuR and microRNAs
leads to lower expression of the shared mRNA. We also describe the regulation of HuR levels by microRNAs as well as
the regulation of microRNA levels by HuR. Finally, we discuss transcriptome-wide analyses of HuR-bound mRNAs with
neighboring microRNA sites, and review the emerging mechanisms whereby microRNAs confer versatility and robustness
to the post-transcriptional outcomes of HuR targets.
Keywords: Ribonucleoprotein complexes, RNA-binding protein, microRNA, post-transcriptional gene regulation, mRNA decay,
translational contro, RISC, post-transcriptional gene, regulation, MicroRNAs, miRNAs.
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