The ubiquitous mRNA-binding protein human antigen R (HuR) and its neuronal relatives (HuB, HuC, HuD)
participate in the post-transcriptional regulation of many AU-rich element-bearing mRNAs. In addition to its originally
described role in controlling mRNA decay, the binding of HuR to target mRNAs can affect many aspects of mRNA processing
including splicing, polyadenylation, intracellular trafficking, translation and modulation of mRNA repression by
miRNAs. In accordance to the growing list of signalling events which are involved in regulating these different HuR functions,
recent data implicate that posttranslational modification, namely protein kinase-triggered phosphorylation of HuR
plays a crucial role in connecting extracellular signal inputs to a specific post-transcriptional program by HuR. Notably, in
addition to directly targeting HuR functions, posttranslational modifications of HuR have a major impact on the sequestration
and binding to various HuR ligand proteins as has been demonstrated e.g. for the 14-3-3 chaperones. However, the
detailed mechanisms of how a specific modification of HuR coordinates different aspects in HuR regulation are currently
poorly understood. Due to the fact that most of the described HuR activities are closely related to its subcellular localization
and the binding to cargo mRNA, this review will focus on these aspects of HuR functions and their control by posttranslational
modification, particularly by HuR phosphorylations by different protein kinases.
Keywords: AU-rich element binding protein, mRNA stability, posttranslational modification, nucleo-cytoplasmic HuR shuttling,
protein kinase C, shuttling, mRNA, AUUUA, AUUUA motif, ARE-dependent mRNA, ARE-dependent mRNA decay.
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