<i>cis</i>‐Acting signals and <i>trans</i>‐acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells

Behar, Leah; Marx, Ruth; Sadot, Einat; Barg, Jacob; Ginzburg, Irith

doi:10.1016/0736-5748(95)00001-w

Cited by 78 publications

(74 citation statements)

References 50 publications

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“…KIF3A belongs to the kinesin superfamily and has been characterized as an MT-based anterograde motor enriched in neuronal axons (Hirokawa, 1998;Hirokawa, 2000;Kondo et al, 1994). A complex between the tau 3′ ALS region and a protein of a similar size to KIF3A was previously detected by a UV crosslinking assay using brain or neuronal cell extracts (Behar et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules

Aronov

Aranda

Behar

et al. 2002

Journal of Cell Science

103

104

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Localization of tau mRNA to the axon requires the axonal localization cis signal (ALS), which is located within the 3′ untranslated region, and trans-acting binding proteins, which are part of the observed granular structures in neuronal cells. In this study, using both biochemical and morphological methods, we show that the granules contain tau mRNA, HuD RNA-binding protein, which stabilizes mRNA, and KIF3A, a member of the kinesin microtubuleassociated motor protein family involved in anterograde transport. The granules are detected along the axon and accumulate in the growth cone. Inhibition of KIF3A expression caused neurite retraction and inhibited tau mRNA axonal targeting. Taken together, these results suggest that HuD and KIF3A proteins are present in the tau mRNA axonal granules and suggest an additional function for the kinesin motor family in the microtubuledependent translocation of RNA granules. Localized tau-GFP expression was blocked by a protein synthesis inhibitor, and upon release from inhibition, nascent tau-GFP 'hot spots' were directly observed in the axon and growth cones. These observations are consistent with local protein synthesis in the axon resulting from the transported tau mRNA.

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Section: Discussionmentioning

confidence: 99%

“…In neuronal cells, tau is found primarily in the cell body and axon. Axonal localization of tau mRNA to the proximal segment of the axon is dependent on 3′ UTR cisacting signals, neuronal proteins and assembled MTs (ArandaAbreu et al, 1999;Aronov et al, 2001;Behar et al, 1995;Litman et al, 1993;Litman et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules

Aronov

Aranda

Behar

et al. 2002

Journal of Cell Science

103

104

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“…Cells were grown to z90% confluence, and cytoplasmic protein extracts were prepared following the method of Behar et al (1995) with modifications. Cells were resuspended in lysis buffer (130 mM NaCl, 5 mM MgCl 2 , 30 mM Tris-HCl pH 7.6 containing 2 mM DTT, 0.5% [v/v] NP-40 and EDTA-free protease inhibitor cocktail [Roche]) and lysed by passing them through a 21-gauge needle seven times.…”

Section: S100 Cell Extractsmentioning

confidence: 99%

Elongation factor 1α binds to the region of the metallothionein-1 mRNA implicated in perinuclear localization—importance of an internal stem–loop

Mickleburgh

Chabanon²,

Nury³

et al. 2006

RNA

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In eukaryotic cells, mRNA localization can provide local protein synthesis. Metallothionein-1 (MT-1) mRNA is associated with the perinuclear cytoskeleton, and this is essential for subsequent nuclear import of the protein. The present study defines the cisacting localization signal and a trans-acting binding protein. Gel retardation and UV cross-linking assays using MT-1 39UTR transcripts and CHO cell extracts revealed formation of a complex containing a ;50-kDa protein. Only localization-positive mutant transcripts competed for binding of this protein. Using an RNA affinity technique, Western blotting, mass spectrometry, and a supershift assay, the protein was identified as Elongation factor 1a (eEF1a). Mutation and deletion analysis showed that two regions, nucleotides 21-36 and 66-76, were required for both binding and localization. RNA-folding prediction combined with chemical and enzymatic probing experiments suggest that these regions are in juxtaposition within a stem/internal loop structure. Mutations that are predicted to alter this structure abrogate protein binding. Our hypothesis is that the cis-acting signal in MT-1 39UTR is formed by this stem/internal loop, that it binds eEF1a, and that eEF1a-cytoskeleton interactions play a role in perinuclear mRNA localization.

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“…This localization is mediated by the tau 3 -UTR (see below) and depends on microtubules (157). Interestingly, in vitro synthesized tau 3 -UTR injected into Xenopus oocytes localizes to the vegetal pole in a pattern identical to Vg1 RNA (158).…”

Section: Directed Cytoplasmic Transport Of Rnamentioning

confidence: 99%

Rna Localization in Development

Bashirullah

Cooperstock

Lipshitz

1998

Annu. Rev. Biochem.

321

191

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Cytoplasmic RNA localization is an evolutionarily ancient mechanism for producing cellular asymmetries. This review considers RNA localization in the context of animal development. Both mRNAs and non-protein-coding RNAs are localized in Drosophila, Xenopus, ascidian, zebrafish, and echinoderm oocytes and embryos, as well as in a variety of developing and differentiated polarized cells from yeast to mammals. Mechanisms used to transport and anchor RNAs in the cytoplasm include vectorial transport out of the nucleus, directed cytoplasmic transport in association with the cytoskeleton, and local entrapment at particular cytoplasmic sites. The majority of localized RNAs are targeted to particular cytoplasmic regions by cis-acting RNA elements; in mRNAs these are almost always in the 3 -untranslated region (UTR). A variety of trans-acting factorsmany of them RNA-binding proteins-function in localization. Developmental functions of RNA localization have been defined in Xenopus, Drosophila, and Saccharomyces cerevisiae. In Drosophila, localized RNAs program the anteroposterior and dorso-ventral axes of the oocyte and embryo. In Xenopus, localized RNAs may function in mesoderm induction as well as in dorso-ventral axis specification. Localized RNAs also program asymmetric cell fates during Drosophila neurogenesis and yeast budding. 335

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cis‐Acting signals and trans‐acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells

Cited by 78 publications

References 50 publications

Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules

Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules

Elongation factor 1α binds to the region of the metallothionein-1 mRNA implicated in perinuclear localization—importance of an internal stem–loop

Rna Localization in Development

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