scholarly journals Dendritic Transport and Localization of Protein Kinase Mζ mRNA

2004 ◽  
Vol 279 (50) ◽  
pp. 52613-52622 ◽  
Author(s):  
Ilham Aliagaevich Muslimov ◽  
Volker Nimmrich ◽  
Alejandro Ivan Hernandez ◽  
Andrew Tcherepanov ◽  
Todd Charlton Sacktor ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Translational Control ◽  
Untranslated Region ◽  
Functional Integration ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Reading Frame ◽  
Cis Acting ◽  
Translational Repressor ◽  
Protein Kinase Mζ

Protein kinase Mζ (PKMζ) is an atypical protein kinase C isoform that has been implicated in the protein synthesis-dependent maintenance of long term potentiation and memory storage in the brain. Synapse-associated kinases are uniquely positioned to promote enduring consolidation of structural and functional modifications at the synapse, provided that kinase mRNA is available on site for local input-specific translation. We now report that the mRNA encoding PKMζ is rapidly transported and specifically localized to synaptodendritic neuronal domains. Transport of PKMζ mRNA is specified by two cis-acting dendritic targeting elements (Mζ DTEs). Mζ DTE1, located at the interface of the 5′-untranslated region and the open reading frame, directs somato-dendritic export of the mRNA. Mζ DTE2, in contrast, is located in the 3′-untranslated region and is required for delivery of the mRNA to distal dendritic segments. Colocalization with translational repressor BC1 RNA in hippocampal dendrites suggests that PKMζ mRNA may be subject to translational control in local domains. Dendritic localization of PKMζ mRNA provides a molecular basis for the functional integration of synaptic signal transduction and translational control pathways.

scholarly journals The MEF2A 3' untranslated region functions as a cis-acting translational repressor.

1997 ◽  
Vol 17 (5) ◽  
pp. 2756-2763 ◽  
Author(s):  
B L Black ◽  
J Lu ◽  
E N Olson
Keyword(s):  
Transcription Factors ◽  
Translational Control ◽  
Untranslated Region ◽  
Binding Activity ◽  
Translational Repression ◽  
Rnase Protection ◽  
Cis Acting ◽  
Translational Repressor

Myocyte enhancer factor 2 (MEF2) proteins serve as important muscle transcription factors. In addition, MEF2 proteins have been shown to potentiate the activity of other cell-type-specific transcription factors found in muscle and brain tissue. While transcripts for MEF2 factors are widely expressed in a variety of cells and tissues, MEF2 proteins and binding activity are largely restricted to skeletal, smooth, and cardiac muscle and to brain. This disparity between MEF2 protein and mRNA expression suggests that translational control may play an important role in regulating MEF2 expression. In an effort to identify sequences within the MEF2A message which control translation, we isolated the mouse MEF2A 3' untranslated region (UTR) and fused it to the chloramphenicol acetyltransferase (CAT) reporter gene. Here, we show by CAT assay that the MEF2A 3' UTR dramatically inhibits CAT gene expression in vivo and that this inhibition is due to an internal region within the highly conserved 3' UTR. RNase protection analyses demonstrated that the steady-state level of CAT mRNA produced in vivo was not affected by fusion of the MEF2A 3' UTR, indicating that the inhibition of CAT activity resulted from translational repression. Furthermore, fusion of the MEF2A 3' UTR to CAT inhibited translation in vitro in rabbit reticulocyte lysates. We also show that the translational repression mediated by the 3' UTR of MEF2A is regulated during muscle cell differentiation. As muscle cells in culture differentiate, the translational inhibition caused by the MEF2A 3' UTR is relaxed. These results demonstrate that the MEF2A 3' UTR functions as a cis-acting translational repressor both in vitro and in vivo and suggest that this repression may contribute to the tissue-restricted expression and binding activity of MEF2A.

Temporal regulation of the Xenopus FGF receptor in development: a translation inhibitory element in the 3′ untranslated region

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1775-1785 ◽  
Author(s):  
E.P. Robbie ◽  
M. Peterson ◽  
E. Amaya ◽  
T.J. Musci
Keyword(s):  
Protein Interactions ◽  
Translational Control ◽  
Untranslated Region ◽  
Rna Stability ◽  
Immature Oocyte ◽  
Translational Repression ◽  
Meiotic Maturation ◽  
Fgf Receptor ◽  
Cis Acting ◽  
Maternal Mrna

Early frog embryogenesis depends on a maternal pool of mRNA to execute critical intercellular signalling events. FGF receptor-1, which is required for normal development, is stored as a stable, untranslated maternal mRNA transcript in the fully grown immature oocyte, but is translationally activated at meiotic maturation. We have identified a short cis-acting element in the FGF receptor 3′ untranslated region that inhibits translation of synthetic mRNA. This inhibitory element is sufficient to inhibit translation of heterologous reporter mRNA in the immature oocyte without changing RNA stability. Deletion of the poly(A) tract or polyadenylation signal sequences does not affect translational inhibition by this element. At meiotic maturation, we observe the reversal of translational repression mediated by the inhibitory element, mimicking that seen with endogenous maternal FGF receptor mRNA at meiosis. In addition, the activation of synthetic transcripts at maturation does not appear to require poly(A) lengthening. We also show that an oocyte cytoplasmic protein specifically binds the 3′ inhibitory element, suggesting that translational repression of Xenopus FGF receptor-1 maternal mRNA in the oocytes is mediated by RNA-protein interactions. These data describe a mechanism of translational control that appears to be independent of poly(A) changes.

Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1129-1138 ◽  
Author(s):  
Y.S. Lie ◽  
P.M. Macdonald
Keyword(s):  
Translational Control ◽  
Untranslated Region ◽  
Rna Binding ◽  
Mrna Translation ◽  
Posterior Pole ◽  
Translational Repression ◽  
Yeast Two Hybrid ◽  
Functional Interaction ◽  
Translational Repressor ◽  
Two Hybrid

The product of the oskar gene directs posterior patterning in the Drosophila oocyte, where it must be deployed specifically at the posterior pole. Proper expression relies on the coordinated localization and translational control of the oskar mRNA. Translational repression prior to localization of the transcript is mediated, in part, by the Bruno protein, which binds to discrete sites in the 3′ untranslated region of the oskar mRNA. To begin to understand how Bruno acts in translational repression, we performed a yeast two-hybrid screen to identify Bruno-interacting proteins. One interactor, described here, is the product of the apontic gene. Coimmunoprecipitation experiments lend biochemical support to the idea that Bruno and Apontic proteins physically interact in Drosophila. Genetic experiments using mutants defective in apontic and bruno reveal a functional interaction between these genes. Given this interaction, Apontic is likely to act together with Bruno in translational repression of oskar mRNA. Interestingly, Apontic, like Bruno, is an RNA-binding protein and specifically binds certain regions of the oskar mRNA 3′ untranslated region.

A conserved 90 nucleotide element mediates translational repression of nanos RNA

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2791-2800 ◽  
Author(s):  
E.R. Gavis ◽  
L. Lunsford ◽  
S.E. Bergsten ◽  
R. Lehmann
Keyword(s):  
Translational Control ◽  
Untranslated Region ◽  
Translational Regulation ◽  
Critical Role ◽  
Rna Localization ◽  
Translational Repression ◽  
Regulatory Function ◽  
Control Element ◽  
Cis Acting ◽  
Localization Signal

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3′ untranslated region. We have identified a discrete translational control element within the nanos 3′ untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3′UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.

scholarly journals Control of eukaryotic protein synthesis by upstream open reading frames in the 5′-untranslated region of an mRNA

2002 ◽  
Vol 367 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Hedda A. MEIJER ◽  
Adri A.M. THOMAS
Keyword(s):  
Translational Control ◽  
Untranslated Region ◽  
Developmental Stages ◽  
Mrna Translation ◽  
Open Reading Frames ◽  
Open Reading Frame ◽  
Internal Ribosome Entry ◽  
Control Of Gene Expression ◽  
Reading Frame ◽  
Upstream Open Reading Frames

Control of gene expression is achieved at various levels. Translational control becomes crucial in the absence of transcription, such as occurs in early developmental stages. One of the initiating events in translation is that the 40S subunit of the ribosome binds the mRNA at the 5′-cap structure and scans the 5′-untranslated region (5′-UTR) for AUG initiation codons. AUG codons upstream of the main open reading frame can induce formation of a translation-competent ribosome that may translate and (i) terminate and re-initiate, (ii) terminate and leave the mRNA, resulting in down-regulation of translation of the main open reading frame, or (iii) synthesize an N-terminally extended protein. In the present review we discuss how upstream AUGs can control the expression of the main open reading frame, and a comparison is made with other elements in the 5′-UTR that control mRNA translation, such as hairpins and internal ribosome entry sites. Recent data indicate the flexibility of controlling translation initiation, and how the mode of ribosome entry on the mRNA as well as the elements in the 5′-UTR can accurately regulate the amount of protein synthesized from a specific mRNA.

scholarly journals Cellular and subcellular localization of PKMζ

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130140 ◽  
Author(s):  
A. Iván Hernández ◽  
William C. Oxberry ◽  
John F. Crary ◽  
Suzanne S. Mirra ◽  
Todd Charlton Sacktor
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Electron Microscopic ◽  
Term Memory

In contrast to protein kinases that participate in long-term potentiation (LTP) induction and memory consolidation, the autonomously active atypical protein kinase C isoform, protein kinase Mzeta (PKMζ), functions in the core molecular mechanism of LTP maintenance and long-term memory storage. Here, using multiple complementary techniques for light and electron microscopic immunolocalization, we present the first detailed characterization of the cellular and subcellular distribution of PKMζ in rat hippocampus and neocortex. We find that PKMζ is widely expressed in forebrain with prominent immunostaining in hippocampal and neocortical grey matter, and weak label in white matter. In hippocampal and cortical pyramidal cells, PKMζ expression is predominantly somatodendritic, and electron microscopy highlights the kinase at postsynaptic densities and in clusters within spines. In addition, nuclear label and striking punctate immunopositive structures in a paranuclear and dendritic distribution are seen by confocal microscopy, occasionally at dendritic bifurcations. PKMζ immunoreactive granules are observed by electron microscopy in cell bodies and dendrites, including endoplasmic reticulum. The widespread distribution of PKMζ in nuclei, nucleoli and endoplasmic reticulum suggests potential roles of this kinase in cell-wide mechanisms involving gene expression, biogenesis of ribosomes and new protein synthesis. The localization of PKMζ within postsynaptic densities and spines suggests sites where the kinase stores information during LTP maintenance and long-term memory.

scholarly journals Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats

2016 ◽  
Vol 36 (15) ◽  
pp. 4313-4324 ◽  
Author(s):  
Sven R.M. Schuette ◽  
Diego Fernández-Fernández ◽  
Thorsten Lamla ◽  
Holger Rosenbrock ◽  
Scott Hobson
Keyword(s):  
Protein Kinase ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Term Potentiation ◽  
Protein Kinase Mζ
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