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Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein

BACKGROUND: Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a...

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Autores principales: Chen, Linan, Dumelie, Jason G, Li, Xiao, Cheng, Matthew HK, Yang, Zhiyong, Laver, John D, Siddiqui, Najeeb U, Westwood, J Timothy, Morris, Quaid, Lipshitz, Howard D, Smibert, Craig A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053848/
https://www.ncbi.nlm.nih.gov/pubmed/24393533
http://dx.doi.org/10.1186/gb-2014-15-1-r4
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author Chen, Linan
Dumelie, Jason G
Li, Xiao
Cheng, Matthew HK
Yang, Zhiyong
Laver, John D
Siddiqui, Najeeb U
Westwood, J Timothy
Morris, Quaid
Lipshitz, Howard D
Smibert, Craig A
author_facet Chen, Linan
Dumelie, Jason G
Li, Xiao
Cheng, Matthew HK
Yang, Zhiyong
Laver, John D
Siddiqui, Najeeb U
Westwood, J Timothy
Morris, Quaid
Lipshitz, Howard D
Smibert, Craig A
author_sort Chen, Linan
collection PubMed
description BACKGROUND: Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. RESULTS: To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug’s target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. CONCLUSIONS: Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism.
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spelling pubmed-40538482014-06-12 Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein Chen, Linan Dumelie, Jason G Li, Xiao Cheng, Matthew HK Yang, Zhiyong Laver, John D Siddiqui, Najeeb U Westwood, J Timothy Morris, Quaid Lipshitz, Howard D Smibert, Craig A Genome Biol Research BACKGROUND: Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. RESULTS: To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug’s target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. CONCLUSIONS: Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism. BioMed Central 2014 2014-01-07 /pmc/articles/PMC4053848/ /pubmed/24393533 http://dx.doi.org/10.1186/gb-2014-15-1-r4 Text en Copyright © 2014 Chen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Chen, Linan
Dumelie, Jason G
Li, Xiao
Cheng, Matthew HK
Yang, Zhiyong
Laver, John D
Siddiqui, Najeeb U
Westwood, J Timothy
Morris, Quaid
Lipshitz, Howard D
Smibert, Craig A
Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title_full Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title_fullStr Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title_full_unstemmed Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title_short Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein
title_sort global regulation of mrna translation and stability in the early drosophila embryo by the smaug rna-binding protein
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053848/
https://www.ncbi.nlm.nih.gov/pubmed/24393533
http://dx.doi.org/10.1186/gb-2014-15-1-r4
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