title: Targeting the multifaceted HuR protein, benefits and caveats.
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.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zucal
authors.forename: Vito
authors.initials: V
authors.lastname: D'Agostino
authors.forename: Rosa
authors.initials: R
authors.lastname: Loffredo
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantelli
authors.lastname: NatthakanThongon
authors.forename: Preet
authors.initials: P
authors.lastname: Lal
authors.forename: Elisa
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Laboratory of Genomic Screening, Centre for Integrative Biology (CIBIO), University of Trento, Via delle regole 101, 38123, Mattarello, Trento, Italy. alessandro.provenzani@unitn.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Provenzani
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger