HuR in the Mammalian Genotoxic Response: Post-Transcriptional Multitasking

A recently evolved class of alternative 3′-terminal exons involved in cell cycle regulation by topoisomerase inhibitors

“…5c,d) 50,51 . Meanwhile, HuR relocates to the cytoplasm, where it regulates the stability and translation of various mRNAs involved in proliferation and apoptosis through binding to 3 0 UTRs 36,47 . Thus, cell responses to DNA damage may involve the coordinated regulation of both nuclear and cytoplasmic sets of transcripts by HuR.…”

“…The second factor, HuR/ELAVL1, is an RNA-binding protein that has long been involved in the regulation of cytoplasmic mRNA stability and translation in response to DNA damage (reviewed by Gorospe 36 ) and more recently in pre-mRNA splicing and polyA site use in the nucleus [37][38][39][40][41][42] . As expected from the anti-correlation data, the depletion of HuR using a specific siRNA in MCF-7 cells (Fig.…”

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

“…9 The RBP HuR, a paraneoplastic antigen, overexpressed in many malignancies including breast cancer, has been implicated as an important RBP which may function as a tumor maintenance gene, facilitating malignant transformation. [10][11][12][13][14][15][16][17] HuR has been shown to regulate genes in multiple areas of the acquired capabilities model, including two pivotal genes involved in angiogenesis, VEGF and HIF1α. [18][19][20][21][22] Increased HuR cytoplasmic expression directly correlates with severity and aggressiveness of many cancers, including those of the breast.…”

miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels

“…First, HuR function is influenced by processes that affect its subcellular localization. HuR is predominantly nuclear, but shuttles between the nucleus and the cytoplasm (17); its accumulation in the cytoplasm is linked to its ability to stabilize and modulate the translation of target mRNAs (7). Several kinases have been implicated in the regulation of HuR abundance in the cytoplasm, including at least two (PKC, Cdk1) that directly phosphorylate HuR (18)(19)(20).…”

“…These include a family of RBPs that modulate protein expression patterns in response to external factors by altering the cytoplasmic fate of target mRNAs, primarily by acting as translation and turnover regulatory (TTR)-RBPs (3,4). HuR is among the most prominent sequence-specific TTR-RBPs influencing the cellular response to stress agents, proliferative signals, immune triggers, and developmental cues (5)(6)(7)(8).…”