PMID:27609837

Citation	Zhang, W, Vreeland, AC and Noy, N (2016) RNA-binding protein HuR regulates nuclear import of protein. J. Cell. Sci. 129:4025-4033
Abstract	The RNA-binding protein HuR binds to elements rich in adenylate and uridylate (AU-rich elements) in target mRNAs and stabilizes them against degradation. The complete spectrum of genes whose expression is regulated by HuR and are the basis for the broad range of cellular functions of the protein is incompletely understood. We show that HuR controls the expression of multiple components of the nuclear import machinery. Consequently, HuR is crucial for the nuclear import of cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to the nuclear retinoic acid receptor (RAR) and whose mobilization to the nucleus is mediated by a 'classical-like' nuclear localization signal (NLS). HuR is also required for heregulin-induced nuclear translocation of the NFκB subunit p65, which contains both classical and non-canonical NLSs. HuR thus regulates the transcriptional activities of both RAR and NFκB. The observations reveal that HuR plays a central role in regulating nuclear import of proteins.
Links	PubMed PMC5117209 Online version:10.1242/jcs.192096
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ELAV1		GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Mouse ELAVL1/Hua(Hur). HuR shuttles between the nucleus and the cytosol but is predominantly nuclear in non-dividing cells (Fig. 1A).	complete CACAO 12229
MOUSE:ELAV1		GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Mouse (ELAV1/Hua) Cytosolic HuR extensively co-localized with the endoplasmic reticulum (ER) marker calnexin, both in the absence and presence of CGP-74514A (Fig. 1A), demonstrating that extranuclear HuR is associated with the ER.	complete CACAO 12230
MOUSE:ELAV1		GO:0048255: mRNA stabilization	ECO:0000314: direct assay evidence used in manual assertion		P		Mouse (ELAV1/Hua/HUR) The half-life of Kpnb1 mRNA was found to be 16.5±0.75 h and 10.2±1.12 h in shCtrl- and shHuR-expressing cells, respectively (Fig. 3F), indicating that this transcript is indeed stabilized by HuR.	complete CACAO 12232
MOUSE:ELAV1		GO:0006606: protein import into nucleus	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Mouse ELAVL1/Hua(Hur) Strikingly, in M2−/− cells with stable reduced expression of HuR, RA induced a discernible shift in the subcellular localization of CRABP2, but this shift did not culminate in nuclear import. Instead, CRABP2 accumulated around the nucleus and did not enter this compartment (Fig. 2A)	complete CACAO 12233
MOUSE:RABP2		GO:0005783: endoplasmic reticulum	ECO:0000314:		C		Mouse CRABP2 Parental cells and cells with reduced expression of HuR were co-immunostained for Flag–CRABP2 and the ER marker calnexin (Fig. 1C). As expected, CRABP2 co-localized with calnexin in parental cells, reflecting its ER association.	complete CACAO 12258
MOUSE:RABP2		GO:0005634: nucleus	ECO:0000314:		C		Mouse CRABP2 Fig. 2. HuR is required for RA-induced nuclear translocation of CRABP2.	complete CACAO 12259
MOUSE:RABP2		GO:0042573: retinoic acid metabolic process	ECO:0000314:		P		Mouse CRABP2/ Cells were treated with RA, immunostained for CRABP2, and imaged. Endogenous CRABP2 in parental MCF-7 cells underwent nuclear translocation in response to RA, which was similar to its behavior in M2−/− cells that ectopically overexpress CRABP2. By contrast, in MCF-7 cells with reduced expression of HuR, treatment with RA resulted in accumulation of CRABP2 around the nucleus but, again, failed to affect complete nuclear import (Fig. 2C).	complete CACAO 12266

References

See Help:References for how to manage references in GONUTS.