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Drosophila Sister-of-Sex-lethal is a repressor of translation

The RNA-binding protein Sex-lethal (Sxl) is an important post-transcriptional regulator of sex determination and dosage compensation in female Drosophila. To prevent the assembly of the MSL dosage compensation complex in female flies, Sxl acts as a repressor of male-specific lethal-2 (msl-2) mRNA tr...

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Autores principales: Moschall, Rebecca, Strauss, Daniela, García-Beyaert, Marina, Gebauer, Fátima, Medenbach, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769743/
https://www.ncbi.nlm.nih.gov/pubmed/29089381
http://dx.doi.org/10.1261/rna.063776.117
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author Moschall, Rebecca
Strauss, Daniela
García-Beyaert, Marina
Gebauer, Fátima
Medenbach, Jan
author_facet Moschall, Rebecca
Strauss, Daniela
García-Beyaert, Marina
Gebauer, Fátima
Medenbach, Jan
author_sort Moschall, Rebecca
collection PubMed
description The RNA-binding protein Sex-lethal (Sxl) is an important post-transcriptional regulator of sex determination and dosage compensation in female Drosophila. To prevent the assembly of the MSL dosage compensation complex in female flies, Sxl acts as a repressor of male-specific lethal-2 (msl-2) mRNA translation. It uses two distinct and mutually reinforcing blocks to translation that operate on the 5′ and 3′ untranslated regions (UTRs) of msl-2 mRNA, respectively. While 5′ UTR-mediated translational control involves an upstream open reading frame, 3′ UTR-mediated regulation strictly requires the co-repressor protein Upstream of N-ras (Unr), which is recruited to the transcript by Sxl. We have identified the protein Sister-of-Sex-lethal (Ssx) as a novel repressor of translation with Sxl-like activity. Both proteins have a comparable RNA-binding specificity and can associate with uracil-rich RNA regulatory elements present in msl-2 mRNA. Moreover, both repress translation when bound to the 5′ UTR of msl-2. However, Ssx is inactive in 3′ UTR-mediated regulation, as it cannot engage the co-repressor protein Unr. The difference in activity maps to the first RNA-recognition motif (RRM) of Ssx. Conversion of three amino acids within this domain into their Sxl counterpart results in a gain of function and repression via the 3′ UTR, allowing detailed insights into the evolutionary origin of the two proteins and into the molecular requirements of an important translation regulatory pathway.
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spelling pubmed-57697432019-02-01 Drosophila Sister-of-Sex-lethal is a repressor of translation Moschall, Rebecca Strauss, Daniela García-Beyaert, Marina Gebauer, Fátima Medenbach, Jan RNA Article The RNA-binding protein Sex-lethal (Sxl) is an important post-transcriptional regulator of sex determination and dosage compensation in female Drosophila. To prevent the assembly of the MSL dosage compensation complex in female flies, Sxl acts as a repressor of male-specific lethal-2 (msl-2) mRNA translation. It uses two distinct and mutually reinforcing blocks to translation that operate on the 5′ and 3′ untranslated regions (UTRs) of msl-2 mRNA, respectively. While 5′ UTR-mediated translational control involves an upstream open reading frame, 3′ UTR-mediated regulation strictly requires the co-repressor protein Upstream of N-ras (Unr), which is recruited to the transcript by Sxl. We have identified the protein Sister-of-Sex-lethal (Ssx) as a novel repressor of translation with Sxl-like activity. Both proteins have a comparable RNA-binding specificity and can associate with uracil-rich RNA regulatory elements present in msl-2 mRNA. Moreover, both repress translation when bound to the 5′ UTR of msl-2. However, Ssx is inactive in 3′ UTR-mediated regulation, as it cannot engage the co-repressor protein Unr. The difference in activity maps to the first RNA-recognition motif (RRM) of Ssx. Conversion of three amino acids within this domain into their Sxl counterpart results in a gain of function and repression via the 3′ UTR, allowing detailed insights into the evolutionary origin of the two proteins and into the molecular requirements of an important translation regulatory pathway. Cold Spring Harbor Laboratory Press 2018-02 /pmc/articles/PMC5769743/ /pubmed/29089381 http://dx.doi.org/10.1261/rna.063776.117 Text en © 2018 Moschall et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Moschall, Rebecca
Strauss, Daniela
García-Beyaert, Marina
Gebauer, Fátima
Medenbach, Jan
Drosophila Sister-of-Sex-lethal is a repressor of translation
title Drosophila Sister-of-Sex-lethal is a repressor of translation
title_full Drosophila Sister-of-Sex-lethal is a repressor of translation
title_fullStr Drosophila Sister-of-Sex-lethal is a repressor of translation
title_full_unstemmed Drosophila Sister-of-Sex-lethal is a repressor of translation
title_short Drosophila Sister-of-Sex-lethal is a repressor of translation
title_sort drosophila sister-of-sex-lethal is a repressor of translation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769743/
https://www.ncbi.nlm.nih.gov/pubmed/29089381
http://dx.doi.org/10.1261/rna.063776.117
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