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.

Role for mRNA localization in translational activation but not spatial restriction of nanos RNA

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 659-669 ◽  
Author(s):  
S.E. Bergsten ◽  
E.R. Gavis
Keyword(s):  
Translational Control ◽  
Rna Localization ◽  
Early Embryo ◽  
Posterior Pole ◽  
Translational Repression ◽  
Control Element ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Body Patterning ◽  
Localization Signal

Patterning of the anterior-posterior body axis during Drosophila development depends on the restriction of Nanos protein to the posterior of the early embryo. Synthesis of Nanos occurs only when maternally provided nanos RNA is localized to the posterior pole by a large, cis-acting signal in the nanos 3′ untranslated region (3′UTR); translation of unlocalized nanos RNA is repressed by a 90 nucleotide Translational Control Element (TCE), also in the 3′UTR. We now show quantitatively that the majority of nanos RNA in the embryo is not localized to the posterior pole but is distributed throughout the cytoplasm, indicating that translational repression is the primary mechanism for restricting production of Nanos protein to the posterior. Through an analysis of transgenes bearing multiple copies of nanos 3′UTR regulatory sequences, we provide evidence that localization of nanos RNA by components of the posteriorly localized germ plasm activates its translation by preventing interaction of nanos RNA with translational repressors. This mutually exclusive relationship between translational repression and RNA localization is mediated by a 180 nucleotide region of the nanos localization signal, containing the TCE. These studies suggest that the ability of RNA localization to direct wild-type body patterning also requires recognition of multiple, unique elements within the nanos localization signal by novel factors. Finally, we propose that differences in the efficiencies with which different RNAs are localized result from the use of temporally distinct localization pathways during oogenesis.

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.

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.

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.

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 common translational control mechanism functions in axial patterning and neuroendocrine signaling inDrosophila

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3325-3334 ◽  
Author(s):  
Ira E. Clark ◽  
Krista C. Dobi ◽  
Heather K. Duchow ◽  
Anna N. Vlasak ◽  
Elizabeth R. Gavis
Keyword(s):  
Gene Expression ◽  
Translational Control ◽  
Ectopic Expression ◽  
Drosophila Embryo ◽  
Control Element ◽  
Molting Cycle ◽  
Axial Patterning ◽  
Cis Acting ◽  
Maternal Mrnas ◽  
Anterior Posterior

Translational repression of maternal nanos (nos) mRNA by a cis-acting Translational Control Element (TCE) in the nos 3′UTR is critical for anterior-posterior patterning of the Drosophila embryo. We show, through ectopic expression experiments, that the nos TCE is capable of repressing gene expression at later stages of development in neuronal cells that regulate the molting cycle. Our results predict additional targets of TCE-mediated repression within the nervous system. They also suggest that mechanisms that regulate maternal mRNAs, like TCE-mediated repression, may function more widely during development to spatially or temporally control gene expression.

RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1233-1243 ◽  
Author(s):  
P.M. Macdonald ◽  
K. Kerr ◽  
J.L. Smith ◽  
A. Leask
Keyword(s):  
Untranslated Region ◽  
Regulatory Element ◽  
Essential Element ◽  
Mrna Localization ◽  
Morphogen Gradient ◽  
Anterior Pole ◽  
Functional Elements ◽  
Cis Acting ◽  
Localization Signal ◽  
Drosophila Embryos

Deployment of the bicoid morphogen gradient in early Drosophila embryos requires the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior localization is mediated by a cis-acting localization signal contained within the 3′ untranslated region of the bicoid mRNA. Here we use a series of bicoid transgenes carrying small deletions in the 3′ untranslated region to survey for functional elements that constitute the localization signal. We identify and characterize one essential element, BLE1, which specifically directs the early steps of localization. In addition, we find that many deletions within the bicoid mRNA 3′ untranslated region impair but do not prevent localization. One such deletion specifically interferes with a later step in localization. Thus the bicoid mRNA localization signal appears to consist of multiple different elements, each responsible for different steps in the localization process.

Multiple cis-acting targeting sequences are required for orb mRNA localization during Drosophila oogenesis

1994 ◽  
Vol 14 (4) ◽  
pp. 2235-2242
Author(s):  
V Lantz ◽  
P Schedl
Keyword(s):  
Untranslated Region ◽  
Germ Line ◽  
Critical Role ◽  
Positional Information ◽  
Mrna Localization ◽  
Early Embryo ◽  
Developmental Systems ◽  
Localization Pattern ◽  
Cis Acting ◽  
Anterior Posterior

The targeting of positional information to specific regions of the oocyte or early embryo is one of the key processes in establishing anterior-posterior and dorsal-ventral polarity. In many developmental systems, this is accomplished by localization of mRNAs. The germ line-specific Drosophila orb gene plays a critical role in defining both axes of the developing oocyte, and its mRNA is localized in a complex pattern during oogenesis. We have identified a 280-bp sequence from the orb 3' untranslated region capable of reproducing this complex localization pattern. Furthermore, we have found that multiple cis-acting elements appear to be required for proper targeting of orb mRNA.

scholarly journals uORFs: Important Cis-Regulatory Elements in Plants

2020 ◽  
Vol 21 (17) ◽  
pp. 6238
Author(s):  
Ting Zhang ◽  
Anqi Wu ◽  
Yaping Yue ◽  
Yu Zhao
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Translational Regulation ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Post Translational Modification ◽  
Cis Acting ◽  
Eukaryotic Mrnas

Gene expression is regulated at many levels, including mRNA transcription, translation, and post-translational modification. Compared with transcriptional regulation, mRNA translational control is a more critical step in gene expression and allows for more rapid changes of encoded protein concentrations in cells. Translation is highly regulated by complex interactions between cis-acting elements and trans-acting factors. Initiation is not only the first phase of translation, but also the core of translational regulation, because it limits the rate of protein synthesis. As potent cis-regulatory elements in eukaryotic mRNAs, upstream open reading frames (uORFs) generally inhibit the translation initiation of downstream major ORFs (mORFs) through ribosome stalling. During the past few years, with the development of RNA-seq and ribosome profiling, functional uORFs have been identified and characterized in many organisms. Here, we review uORF identification, uORF classification, and uORF-mediated translation initiation. More importantly, we summarize the translational regulation of uORFs in plant metabolic pathways, morphogenesis, disease resistance, and nutrient absorption, which open up an avenue for precisely modulating the plant growth and development, as well as environmental adaption. Additionally, we also discuss prospective applications of uORFs in plant breeding.

scholarly journals Rapid Deadenylation and Poly(A)-Dependent Translational Repression Mediated by the Caenorhabditis elegans tra-2 3′ Untranslated Region in XenopusEmbryos

2000 ◽  
Vol 20 (6) ◽  
pp. 2129-2137 ◽  
Author(s):  
Sunnie R. Thompson ◽  
Elizabeth B. Goodwin ◽  
Marvin Wickens
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Translational Control ◽  
Untranslated Region ◽  
Specific Binding ◽  
Translational Repression ◽  
Female Development ◽  
C Elegans ◽  
Egg Extracts ◽  
Eukaryotic Mrnas

ABSTRACT The 3′ untranslated region (3′UTR) of many eukaryotic mRNAs is essential for their control during early development. Negative translational control elements in 3′UTRs regulate pattern formation, cell fate, and sex determination in a variety of organisms.tra-2 mRNA in Caenorhabditis elegans is required for female development but must be repressed to permit spermatogenesis in hermaphrodites. Translational repression oftra-2 mRNA in C. elegans is mediated by tandemly repeated elements in its 3′UTR; these elements are called TGEs (for tra-2 and GLI element). To examine the mechanism of TGE-mediated repression, we first demonstrate that TGE-mediated translational repression occurs in Xenopus embryos and thatXenopus egg extracts contain a TGE-specific binding factor. Translational repression by the TGEs requires that the mRNA possess a poly(A) tail. We show that in C. elegans, the poly(A) tail of wild-type tra-2 mRNA is shorter than that of a mutant mRNA lacking the TGEs. To determine whether TGEs regulate poly(A) length directly, synthetic tra-2 3′UTRs with and without the TGEs were injected into Xenopus embryos. We find that TGEs accelerate the rate of deadenylation and permit the last 15 adenosines to be removed from the RNA, resulting in the accumulation of fully deadenylated molecules. We conclude that TGE-mediated translational repression involves either interference with poly(A)'s function in translation and/or regulated deadenylation.

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