Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons

Tiruchinapalli, Dhanrajan; Ehlers, Michael; Keene, Jack D.

doi:10.4161/rna.5.3.6782

Cited by 48 publications

(63 citation statements)

References 71 publications

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“…Despite the extensive regional variability in the expression of Elavl/Hu proteins 6 in the CNS (Supplementary Figure 1), both HuR and nElavls are present in the hippocampus formation as indicated by the signals detected with anti-HuR and anti-HuD antisera ( Figure 1a); we selected to focus primarily on HuD as a representative of nElavls given prior indications on its involvement in the activity-dependent responses of pyramidal neurons. 7,13 HuR's expression is strong in the CA1 and DG regions, but lower in the CA2/CA3 regions. In contrast, the expression of HuD is strong in the CA2/CA3 regions, but low in the CA1 and DG regions.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotection requires the functions of the RNA-binding protein HuR

et al. 2014

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Alterations in the functions of neuronal RNA-binding proteins (RBPs) can contribute to neurodegenerative diseases. However, neurons also express a set of widely distributed RBPs that may have developed specialized functions. Here, we show that the ubiquitous member of the otherwise neuronal Elavl/Hu family of RNA-binding proteins, Elavl1/HuR, has a neuroprotective role. Mice engineered to lack exclusively HuR in the hippocampal neurons of the central nervous system (CNS), maintain physiologic levels of neuronal Elavls and develop a partially diminished seizure response following strong glutamatergic excitation; however, they display an exacerbated neurodegenerative response subsequent to the initial excitotoxic event. This response was phenocopied in hippocampal cells devoid of ionotropic glutamate receptors in which the loss of HuR results in enhanced mitochondrial dysfunction, oxidative damage and programmed necrosis solely after glutamate challenge. The molecular dissection of HuR and nElavl mRNA targets revealed the existence of a HuR-restricted posttranscriptional regulon that failed in HuR-deficient neurons and is involved in cellular energetics and oxidation defense. Thus, HuR acts as a specialized controller of oxidative metabolism in neurons to confer protection from neurodegeneration.

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Section: Resultsmentioning

confidence: 99%

Neuroprotection requires the functions of the RNA-binding protein HuR

et al. 2014

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“…Firstly, PABP is present in neuronal regions distant from the cell body, e.g. dendrites, axonal filopodia and terminal growth cones [62,63] and co-localizes in punta/granules with RNA-binding proteins, such as the wellcharacterized HuD [64], implicated in activity-dependent localized translation, as well as with putative regulatory factors, e.g. Makorin RING zinc finger protein (MKNR)1 [65], with which it interacts.…”

Section: Pabp and Localized Translationmentioning

confidence: 99%

Poly(A)-binding proteins and mRNA localization: who rules the roost?

Gray

Hrabálková

Scanlon

et al. 2015

Biochemical Society Transactions

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RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals.

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“…For example, two target mRNAs of HuD involved in axonal outgrowth, namely GAP-43 and Tau, were found to colocalize with HuD protein and polysomes in growth cones during neuronal differentiation (Smith et al 2004;Atlas et al 2007). Co-IP and immunocytochemistry experiments revealed that HuD interacts with a host of mRNP components involved in transport and translation in the cytoplasm and neurites such as the motor protein KIF3A (Aronov et al 2002), IGF-II mRNA binding protein 1 (IMP-1) (Atlas et al 2004(Atlas et al , 2007, survival of motor neuron (SMN) (Hubers et al 2010;Akten et al 2011;Fallini et al 2011), poly(A) binding protein (PABP), translation initiation factor 4E (eEF4E) (Tiruchinapalli et al 2008b) and the microtubule-associated component MAP1B (Fujiwara et al 2011b). Various conditions, including KCl depolarization of primary hippocampal neurons, cocaine, or seizure treatment of mice and phorbol ester or bryostatin-1 application to human neuroblastoma (NB) cells, result in an augmented abundance of HuD, its redistribution to neurites, and its increased association with mRNAs and mRNP components (Pascale et al 2005;Tiruchinapalli et al 2008a,b).…”

Section: Mrna Localization and Translationmentioning

confidence: 99%

Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction

Bronicki

Jasmin

2013

RNA

107

118

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Precise control of messenger RNA (mRNA) processing and abundance are increasingly being recognized as critical for proper spatiotemporal gene expression, particularly in neurons. These regulatory events are governed by a large number of transacting factors found in neurons, most notably RNA-binding proteins (RBPs) and micro-RNAs (miRs), which bind to specific cisacting elements or structures within mRNAs. Through this binding mechanism, trans-acting factors, particularly RBPs, control all aspects of mRNA metabolism, ranging from altering the transcription rate to mediating mRNA degradation. In this context the best-characterized neuronal RBP, the Hu/ELAVl family member HuD, is emerging as a key component in multiple regulatory processes-including pre-mRNA processing, mRNA stability, and translation-governing the fate of a substantial amount of neuronal mRNAs. Through its ability to regulate mRNA metabolism of diverse groups of functionally similar genes, HuD plays important roles in neuronal development and function. Furthermore, compelling evidence indicates supplementary roles for HuD in neuronal plasticity, in particular, recovery from axonal injury, learning and memory, and multiple neurological diseases. The purpose of this review is to provide a detailed overview of the current knowledge surrounding the expression and roles of HuD in the nervous system. Additionally, we outline the present understanding of the molecular mechanisms presiding over the localization, abundance, and function of HuD in neurons.

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Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons

Cited by 48 publications

References 71 publications

Neuroprotection requires the functions of the RNA-binding protein HuR

Neuroprotection requires the functions of the RNA-binding protein HuR

Poly(A)-binding proteins and mRNA localization: who rules the roost?

Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction

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