Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades.
Steroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003085&type=printable |
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| author | Robert J Ihry Anne L Sapiro Arash Bashirullah |
| author_facet | Robert J Ihry Anne L Sapiro Arash Bashirullah |
| author_sort | Robert J Ihry |
| collection | DOAJ |
| description | Steroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the evolutionarily conserved DEAD box RNA helicase belle/DDX3 that disrupts a subset of responses to the steroid hormone ecdysone during Drosophila melanogaster metamorphosis. We demonstrate that belle directly regulates translation of E74A, an ets transcription factor and critical component of the ecdysone-induced transcriptional cascade. Although E74A mRNA accumulates to abnormally high levels in belle mutant tissues, no E74A protein is detectable, resulting in misregulation of E74A-dependent ecdysone response genes. The accumulation of E74A mRNA in belle mutant salivary glands is a result of auto-regulation, fulfilling a prediction made by Ashburner nearly 40 years ago. In this model, Ashburner postulates that, in addition to regulating secondary response genes, protein products of primary response genes like E74A also inhibit their own ecdysone-induced transcription. Moreover, although ecdysone-triggered transcription of E74A appears to be ubiquitous during metamorphosis, belle-dependent translation of E74A mRNA is spatially restricted. These results demonstrate that translational control plays a critical, and previously unknown, role in refining transcriptional responses to the steroid hormone ecdysone. |
| format | Article |
| id | doaj-art-0fcfc4f0d80a4b458c3bb3ee08b4d99d |
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| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-0fcfc4f0d80a4b458c3bb3ee08b4d99d2025-08-20T02:15:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01811e100308510.1371/journal.pgen.1003085Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades.Robert J IhryAnne L SapiroArash BashirullahSteroid hormones act, through their respective nuclear receptors, to regulate target gene expression. Despite their critical role in development, physiology, and disease, however, it is still unclear how these systemic cues are refined into tissue-specific responses. We identified a mutation in the evolutionarily conserved DEAD box RNA helicase belle/DDX3 that disrupts a subset of responses to the steroid hormone ecdysone during Drosophila melanogaster metamorphosis. We demonstrate that belle directly regulates translation of E74A, an ets transcription factor and critical component of the ecdysone-induced transcriptional cascade. Although E74A mRNA accumulates to abnormally high levels in belle mutant tissues, no E74A protein is detectable, resulting in misregulation of E74A-dependent ecdysone response genes. The accumulation of E74A mRNA in belle mutant salivary glands is a result of auto-regulation, fulfilling a prediction made by Ashburner nearly 40 years ago. In this model, Ashburner postulates that, in addition to regulating secondary response genes, protein products of primary response genes like E74A also inhibit their own ecdysone-induced transcription. Moreover, although ecdysone-triggered transcription of E74A appears to be ubiquitous during metamorphosis, belle-dependent translation of E74A mRNA is spatially restricted. These results demonstrate that translational control plays a critical, and previously unknown, role in refining transcriptional responses to the steroid hormone ecdysone.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003085&type=printable |
| spellingShingle | Robert J Ihry Anne L Sapiro Arash Bashirullah Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. PLoS Genetics |
| title | Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. |
| title_full | Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. |
| title_fullStr | Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. |
| title_full_unstemmed | Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. |
| title_short | Translational control by the DEAD Box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. |
| title_sort | translational control by the dead box rna helicase belle regulates ecdysone triggered transcriptional cascades |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003085&type=printable |
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