Title:Targeting the Multifaceted HuR Protein, Benefits and Caveats
Volume: 16
Issue: 5
Author(s): Chiara Zucal, Vito D’Agostino, Rosa Loffredo, Barbara Mantelli, NatthakanThongon, Preet Lal, Elisa Latorre and Alessandro Provenzani
Affiliation:
Keywords:
ELAVL1, HuR, HuR activator, HuR animal models, HuR druggability, HuR inhibitor, post-transcriptional control.
Abstract: The RNA-binding protein (RBP) HuR is one of the most widely studied regulators of the eukaryotic posttranscriptional
gene expression and it plays a physiological role in mediating the cellular response to apoptotic, proliferating
and survival stimuli. Following physiological or stress stimuli, HuR protein binds to Adenylate-Urydinilate rich elements
(AREs) generally contained in the 3’UTR of transcripts, then it shuttles from the nucleus to the cytoplasm and regulates
the half-life and/or translation of cargo mRNAs. Derangements in sub-cellular localization and expression of HuR
have been associated with the pathophysiology of many diseases and this protein has been proposed as a potential drug
target. Recent findings also re-evaluated HuR as a splicing and polyadenylation factor, expanding its spectrum of functional
activity up to the maturation of pre-mRNAs. In this review, we generate a comprehensive picture of HuR functionality
to discuss the implications of considering HuR as pharmacological target and the detrimental or positive impact that
can be expected upon its modulation. Firstly, we focus on the recent findings about the mechanistic role of HuR in the nucleus
and in the regulation of long non coding RNAs; then we describe the animal models and the clinical association and
significance in cancer; finally, we have reviewed the pharmacological tools that influence HuR’s post-transcriptional control
and the efforts made to identify specific HuR inhibitors.