The Experts below are selected from a list of 21843 Experts worldwide ranked by ideXlab platform
Wei Chen - One of the best experts on this subject based on the ideXlab platform.
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Pervasive isoform‐specific Translational Regulation via alternative transcription start sites in mammals
Molecular Systems Biology, 2016Co-Authors: Xi Wang, Claudia Quedenau, Wei ChenAbstract:Transcription initiated at alternative sites can produce mRNA isoforms with different 5'UTRs, which are potentially subjected to differential Translational Regulation. However, the prevalence of such isoform-specific Translational control across mammalian genomes is currently unknown. By combining polysome profiling with high-throughput mRNA 5' end sequencing, we directly measured the Translational status of mRNA isoforms with distinct start sites. Among 9,951 genes expressed in mouse fibroblasts, we identified 4,153 showed significant initiation at multiple sites, of which 745 genes exhibited significant isoform-divergent translation. Systematic analyses of the isoform-specific translation revealed that isoforms with longer 5'UTRs tended to translate less efficiently. Further investigation of cis-elements within 5'UTRs not only provided novel insights into the Regulation by known sequence features, but also led to the discovery of novel regulatory sequence motifs. Quantitative models integrating all these features explained over half of the variance in the observed isoform-divergent translation. Overall, our study demonstrated the extensive Translational Regulation by usage of alternative transcription start sites and offered comprehensive understanding of Translational Regulation by diverse sequence features embedded in 5'UTRs.
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pervasive isoform specific Translational Regulation via alternative transcription start sites in mammals
Molecular Systems Biology, 2016Co-Authors: Xi Wang, Claudia Quedenau, Wei ChenAbstract:Transcription initiated at alternative sites can produce mRNA isoforms with different 5'UTRs, which are potentially subjected to differential Translational Regulation. However, the prevalence of such isoform-specific Translational control across mammalian genomes is currently unknown. By combining polysome profiling with high-throughput mRNA 5' end sequencing, we directly measured the Translational status of mRNA isoforms with distinct start sites. Among 9,951 genes expressed in mouse fibroblasts, we identified 4,153 showed significant initiation at multiple sites, of which 745 genes exhibited significant isoform-divergent translation. Systematic analyses of the isoform-specific translation revealed that isoforms with longer 5'UTRs tended to translate less efficiently. Further investigation of cis-elements within 5'UTRs not only provided novel insights into the Regulation by known sequence features, but also led to the discovery of novel regulatory sequence motifs. Quantitative models integrating all these features explained over half of the variance in the observed isoform-divergent translation. Overall, our study demonstrated the extensive Translational Regulation by usage of alternative transcription start sites and offered comprehensive understanding of Translational Regulation by diverse sequence features embedded in 5'UTRs.
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Extensive allele-specific Translational Regulation in hybrid mice.
Molecular Systems Biology, 2015Co-Authors: Xi Wang, Erik Mcshane, Henrik Zauber, Matthias Selbach, Wei ChenAbstract:Translational Regulation is mediated through the interaction between diffusible trans-factors and cis-elements residing within mRNA transcripts. In contrast to extensively studied transcriptional Regulation, cis-Regulation on translation remains underexplored. Using deep sequencing-based transcriptome and polysome profiling, we globally profiled allele-specific Translational efficiency for the first time in an F1 hybrid mouse. Out of 7,156 genes with reliable quantification of both alleles, we found 1,008 (14.1%) exhibiting significant allelic divergence in Translational efficiency. Systematic analysis of sequence features of the genes with biased allelic translation revealed that local RNA secondary structure surrounding the start codon and proximal out-of-frame upstream AUGs could affect Translational efficiency. Finally, we observed that the cis-effect was quantitatively comparable between transcriptional and Translational Regulation. Such effects in the two regulatory processes were more frequently compensatory, suggesting that the Regulation at the two levels could be coordinated in maintaining robustness of protein expression.
Xi Wang - One of the best experts on this subject based on the ideXlab platform.
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Pervasive isoform‐specific Translational Regulation via alternative transcription start sites in mammals
Molecular Systems Biology, 2016Co-Authors: Xi Wang, Claudia Quedenau, Wei ChenAbstract:Transcription initiated at alternative sites can produce mRNA isoforms with different 5'UTRs, which are potentially subjected to differential Translational Regulation. However, the prevalence of such isoform-specific Translational control across mammalian genomes is currently unknown. By combining polysome profiling with high-throughput mRNA 5' end sequencing, we directly measured the Translational status of mRNA isoforms with distinct start sites. Among 9,951 genes expressed in mouse fibroblasts, we identified 4,153 showed significant initiation at multiple sites, of which 745 genes exhibited significant isoform-divergent translation. Systematic analyses of the isoform-specific translation revealed that isoforms with longer 5'UTRs tended to translate less efficiently. Further investigation of cis-elements within 5'UTRs not only provided novel insights into the Regulation by known sequence features, but also led to the discovery of novel regulatory sequence motifs. Quantitative models integrating all these features explained over half of the variance in the observed isoform-divergent translation. Overall, our study demonstrated the extensive Translational Regulation by usage of alternative transcription start sites and offered comprehensive understanding of Translational Regulation by diverse sequence features embedded in 5'UTRs.
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pervasive isoform specific Translational Regulation via alternative transcription start sites in mammals
Molecular Systems Biology, 2016Co-Authors: Xi Wang, Claudia Quedenau, Wei ChenAbstract:Transcription initiated at alternative sites can produce mRNA isoforms with different 5'UTRs, which are potentially subjected to differential Translational Regulation. However, the prevalence of such isoform-specific Translational control across mammalian genomes is currently unknown. By combining polysome profiling with high-throughput mRNA 5' end sequencing, we directly measured the Translational status of mRNA isoforms with distinct start sites. Among 9,951 genes expressed in mouse fibroblasts, we identified 4,153 showed significant initiation at multiple sites, of which 745 genes exhibited significant isoform-divergent translation. Systematic analyses of the isoform-specific translation revealed that isoforms with longer 5'UTRs tended to translate less efficiently. Further investigation of cis-elements within 5'UTRs not only provided novel insights into the Regulation by known sequence features, but also led to the discovery of novel regulatory sequence motifs. Quantitative models integrating all these features explained over half of the variance in the observed isoform-divergent translation. Overall, our study demonstrated the extensive Translational Regulation by usage of alternative transcription start sites and offered comprehensive understanding of Translational Regulation by diverse sequence features embedded in 5'UTRs.
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Extensive allele-specific Translational Regulation in hybrid mice.
Molecular Systems Biology, 2015Co-Authors: Xi Wang, Erik Mcshane, Henrik Zauber, Matthias Selbach, Wei ChenAbstract:Translational Regulation is mediated through the interaction between diffusible trans-factors and cis-elements residing within mRNA transcripts. In contrast to extensively studied transcriptional Regulation, cis-Regulation on translation remains underexplored. Using deep sequencing-based transcriptome and polysome profiling, we globally profiled allele-specific Translational efficiency for the first time in an F1 hybrid mouse. Out of 7,156 genes with reliable quantification of both alleles, we found 1,008 (14.1%) exhibiting significant allelic divergence in Translational efficiency. Systematic analysis of sequence features of the genes with biased allelic translation revealed that local RNA secondary structure surrounding the start codon and proximal out-of-frame upstream AUGs could affect Translational efficiency. Finally, we observed that the cis-effect was quantitatively comparable between transcriptional and Translational Regulation. Such effects in the two regulatory processes were more frequently compensatory, suggesting that the Regulation at the two levels could be coordinated in maintaining robustness of protein expression.
B. Suess - One of the best experts on this subject based on the ideXlab platform.
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Tetracycline-aptamer-mediated Translational Regulation in yeast
Molecular microbiology, 2003Co-Authors: S. Hanson, J. E G McCarthy, B. Fink, Karine Berthelot, B. SuessAbstract:We describe post-transcriptional gene Regulation in yeast based on direct RNA-ligand interaction. Tetracycline-dependent Translational Regulation could be imposed via specific aptamers inserted at two different positions in the 5' untranslated region (5'UTR). Translation in vivo was suppressed up to ninefold upon addition of tetracycline. Repression via an aptamer located near the start codon (cap-distal) in the 5'UTR was more effective than repression via a cap-proximal position. On the other hand, suppression in a cell-free system reached maximally 50-fold and was most effective via a cap-proximal aptamer. Examination of the kinetics of tetracycline-dependent Translational inhibition in vitro revealed that preincubation of tetracycline and mRNA before starting translation led not only to the fastest onset of inhibition but also the most effective repression. The differences between the behaviour of the regulatory system in vivo and in vitro are likely to be related to distinct properties of mRNP structure and mRNA accessibility in intact cells as opposed to cell-extracts. Tetracycline-dependent Regulation was also observed after insertion of an uORF sequence upstream of the aptamer, indicating that our system also targets reinitiating ribosomes. Polysomal gradient analyses provided insight into the mechanism of Regulation. Cap-proximal insertion inhibits binding of the 43S complex to the cap structure whereas start-codon-proximal aptamers interfere with formation of the 80S ribosome, probably by blocking the scanning preinitiation complex
Satu Oltedal - One of the best experts on this subject based on the ideXlab platform.
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mechanism and importance of post Translational Regulation of nitrate reductase
Journal of Experimental Botany, 2004Co-Authors: Cathrine Lillo, Christian Meyer, Fiona Provan, Satu OltedalAbstract:In higher plants, nitrate reductase (NR) is inactivated by the phosphorylation of a conserved Ser residue and binding of 14-3-3 proteins in the presence of divalent cations or polyamines. A transgenic Nicotiana plumbaginifolia line (S521) has been constructed where the regulatory, conserved Ser 521 of tobacco NR (corresponding to Ser 534 in Arabidopsis) was mutated into Asp. This mutation resulted in the complete abolition of activation/inactivation in response to light/dark transitions or other treatments known to regulate the activation state of NR. Analysis of the transgenic plants showed that, under certain conditions, when whole plants or cut tissues are exposed to high nitrate supply, post-Translational Regulation is necessary to avoid nitrite accumulation. Abolition of the post-Translational Regulation of NR also results in an increased flux of nitric oxide from the leaves and roots. In view of the results obtained from examining the different transgenic N. plumbaginifolia lines, compartmentation of nitrate into an active metabolic pool and a large storage pool appears to be an important factor for regulating nitrate reduction. The complex Regulation of nitrate reduction is likely to have evolved not only to optimize nitrogen assimilation, but also to prevent and control the formation of toxic, and possibly regulatory, products of NR activities. Phosphorylation of NR has previously been found to influence the degradation of NR in spinach leaves and Arabidopsis cell cultures. However, experiments with whole plants of N. plumbaginifolia, Arabidopsis ,o r squash are in favour of NR degradation being the same in light and darkness and independent of phosphorylation at the regulatory Ser.
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Mechanism and importance of post‐Translational Regulation of nitrate reductase
Journal of Experimental Botany, 2004Co-Authors: Cathrine Lillo, Christian Meyer, Fiona Provan, Satu OltedalAbstract:In higher plants, nitrate reductase (NR) is inactivated by the phosphorylation of a conserved Ser residue and binding of 14-3-3 proteins in the presence of divalent cations or polyamines. A transgenic Nicotiana plumbaginifolia line (S521) has been constructed where the regulatory, conserved Ser 521 of tobacco NR (corresponding to Ser 534 in Arabidopsis) was mutated into Asp. This mutation resulted in the complete abolition of activation/inactivation in response to light/dark transitions or other treatments known to regulate the activation state of NR. Analysis of the transgenic plants showed that, under certain conditions, when whole plants or cut tissues are exposed to high nitrate supply, post-Translational Regulation is necessary to avoid nitrite accumulation. Abolition of the post-Translational Regulation of NR also results in an increased flux of nitric oxide from the leaves and roots. In view of the results obtained from examining the different transgenic N. plumbaginifolia lines, compartmentation of nitrate into an active metabolic pool and a large storage pool appears to be an important factor for regulating nitrate reduction. The complex Regulation of nitrate reduction is likely to have evolved not only to optimize nitrogen assimilation, but also to prevent and control the formation of toxic, and possibly regulatory, products of NR activities. Phosphorylation of NR has previously been found to influence the degradation of NR in spinach leaves and Arabidopsis cell cultures. However, experiments with whole plants of N. plumbaginifolia, Arabidopsis ,o r squash are in favour of NR degradation being the same in light and darkness and independent of phosphorylation at the regulatory Ser.
Paul Lasko - One of the best experts on this subject based on the ideXlab platform.
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Translational Regulation and rna localization in drosophila oocytes and embryos
Annual Review of Genetics, 2001Co-Authors: Oona Johnstone, Paul LaskoAbstract:▪ Abstract Translational control is a prevalent means of gene Regulation during Drosophila oogenesis and embryogenesis. Multiple maternal mRNAs are localized within the oocyte, and this localization is often coupled to their Translational Regulation. Subsequently, Translational control allows maternally deposited mRNAs to direct the early stages of embryonic development. In this review we outline some general mechanisms of Translational Regulation and mRNA localization that have been uncovered in various model systems. Then we focus on the posttranscriptional Regulation of four maternal transcripts in Drosophila that are localized during oogenesis and are critical for embryonic patterning: bicoid (bcd), nanos (nos), oskar (osk), and gurken (grk). Cis- and trans-acting factors required for the localization and Translational control of these mRNAs are discussed along with potential mechanisms for their Regulation.
