Complex formation of the neuron-specific ELAV-like Hu RNA-binding proteins

Kasashima, Katsumi; Sakashita, Eiji; Saito, Kuniaki; Sakamoto, Hiroshi

doi:10.1093/nar/gkf567

Cited by 62 publications

(81 citation statements)

References 44 publications

(30 reference statements)

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“…Accordingly, we observed reduced binding of neuronal Hu proteins to the ARE using various binding assays. In addition to decreased HuD expression, the observed decrease in HuD binding may also result from post-translational modification of HuD, or from interactions with other RNA-binding proteins or structural proteins (Kasashima et al, 1999(Kasashima et al, , 2002Pascale et al, 2004). For instance, during neuronal differentiation, HuD binding activity can be controlled by the protein kinase C signaling pathway (Mobarak et al, 2000;Pascale et al, 2005) or through methylation by the methyltransferase CARM1 (coactivator-associated methyltransferase 1) (Fujiwara et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in the superior cervical ganglion (SCG); however, the molecular events involved in this response remain unknown. Here, we first examined AChE mRNA levels in the brain of transgenic mice that overexpress human HuD. Both in situ hybridization and reverse transcription-PCR demonstrated that AChE transcript levels were increased by more than twofold in the hippocampus of HuD transgenic mice. Additionally, direct interaction between the HuD transgene product and AChE mRNA was observed. Next, we examined the role of HuD in regulating AChE expression in intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE mRNA levels resulted from changes in the stability of presynthesized transcripts. A combination of approaches performed using the region that directly encompasses an adenylate and uridylate (AU)-rich element within the AChE 3Ј-untranslated region demonstrated a decrease in RNA-protein complexes in response to axotomy of the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD transcript and protein levels also decreased. Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy. Together, the results of this study demonstrate that AChE expression in neurons of the rat SCG is regulated via post-transcriptional mechanisms that involve the AU-rich element and HuD.

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Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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“…This effect was observed only when HuR was overexpressed, which may indicate that the activity of HuR depends on the formation of multimeric complexes on its RNA target. In fact, it has been shown recently that Hu proteins can multimerize and retain their RNA binding properties in mammalian cells (60).…”

Section: Cd83 Mrna Contains a Defined Hur-bindingmentioning

confidence: 99%

Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element

Prechtel

Chemnitz

Schirmer

et al. 2006

Journal of Biological Chemistry

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Dendritic cells (DCs) 3 are the most potent antigen-presenting cells of the immune system and are specialized to sensitize helper and killer T cells during the induction of T cell-mediated immunity (1, 2). In fact, DCs are the only antigen-presenting cells that are able to stimulate naive CD4 ϩ and CD8 ϩ T cells and are therefore referred to as "nature's adjuvant."The CD83 molecule is to date the best known marker for fully mature DCs because CD83 is predominantly expressed on the surface of dendritic lineage cells and cannot be detected on immature DC precursors (3-5). Although its exact function remains to be determined, the fact that CD83 expression is activated during DC maturation, together with co-stimulatory molecules such as CD80 and CD86, suggests a functionally important role for CD83 in DC-mediated T cell immunity (6, 7). This notion is also supported by the fact that inhibition of CD83 expression during DC maturation reduces the T cell stimulatory capacity of these DCs in allo-mixed leukocyte reactions (8). A study using the soluble extracellular domain of CD83 has provided the first direct evidence that this specific surface molecule is indeed functionally important for T cell activation; the soluble CD83 protein completely inhibited DC-mediated T cell stimulation in a concentration-dependent manner in vitro (9). These data were subsequently confirmed in an independent study by using CD83-Ig fusion protein (10). Thus, CD83 appears to play an important functional role in the regulation of DC-mediated T cell-specific immune responses. Therefore, the investigation of the regulation of CD83 expression may provide novel opportunities to modulate DC activity and subsequently DC-mediated immune responses.

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“…These included HuR, a member of the Drosophila ELAV family, and poly(C)-binding protein (CP1) (27). Both HuR and HuD are known to bind to AU-rich elements in the 3Ј-UTR and to stabilize mRNA (30). Studies on TNF-␣ production in macrophages found that two proteins (TIA-1 (T cell intracellular antigen) and TIAR) bind to the 3Ј-UTR of mRNA for TNF-␣ and silenced its translation.…”

Section: Identification Of a 23-base Rna Fragment From The 3ј-utr Of mentioning

confidence: 99%

Translational Control of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Death Receptor Expression in Melanoma Cells

Zhang¹,

Zhang²,

Borrow³

et al. 2004

Journal of Biological Chemistry

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In the present study, it was found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-R2 protein expression did not correlate with mRNA expression in melanoma cell lines. In particular, early passage primary cultures from patients had low TRAIL-R2 protein expression compared with later passage cultures although TRAIL-R2 mRNA expression was similar in early and late passages. Similarly, cell lines made resistant to TRAIL by cultures in TRAIL had low TRAIL-R2 protein expression but normal levels of mRNA for TRAIL-R2. Expression from a luciferase reporter gene construct with the 3-untranslated region (UTR) (but not the 5-UTR) of TRAIL-R2 was suppressed when transfected into the TRAIL-selected (resistant) melanoma lines compared with that seen in the parental (sensitive) lines. Similar results were seen in early passage (resistant) cultures compared with late passage (sensitive) primary melanoma cultures. RNA gel shift assays demonstrated protein(s) binding to the 3-UTR of TRAIL-R2 mRNA that were more evident in TRAIL-resistant cultures with low TRAIL-R2 protein expression. A 23-base fragment of the 3-UTR inhibited binding of the proteins to the 3-UTR, and a probe using this fragment bound to proteins in TRAIL-selected melanoma lines and early passage isolates of melanoma. Binding of the 3-UTR probe to the cytosolic protein(s) was induced by exposure to TRAIL and was lost from the TRAIL selected lines 2-3 days after withdrawal of TRAIL from the cultures. These results are consistent with post-transcriptional regulation of TRAIL-R2 expression by cytosolic proteins induced by TRAIL that bind to the 3-UTR region of TRAIL-R2 mRNA.

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Complex formation of the neuron-specific ELAV-like Hu RNA-binding proteins

Cited by 62 publications

References 44 publications

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element

Translational Control of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Death Receptor Expression in Melanoma Cells

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