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Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation
Makorins are evolutionary conserved proteins that contain C(3)H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specif...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001992/ https://www.ncbi.nlm.nih.gov/pubmed/31978041 http://dx.doi.org/10.1371/journal.pgen.1008581 |
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author | Dold, Annabelle Han, Hong Liu, Niankun Hildebrandt, Andrea Brüggemann, Mirko Rücklé, Cornelia Hänel, Heike Busch, Anke Beli, Petra Zarnack, Kathi König, Julian Roignant, Jean-Yves Lasko, Paul |
author_facet | Dold, Annabelle Han, Hong Liu, Niankun Hildebrandt, Andrea Brüggemann, Mirko Rücklé, Cornelia Hänel, Heike Busch, Anke Beli, Petra Zarnack, Kathi König, Julian Roignant, Jean-Yves Lasko, Paul |
author_sort | Dold, Annabelle |
collection | PubMed |
description | Makorins are evolutionary conserved proteins that contain C(3)H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR. |
format | Online Article Text |
id | pubmed-7001992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70019922020-02-18 Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation Dold, Annabelle Han, Hong Liu, Niankun Hildebrandt, Andrea Brüggemann, Mirko Rücklé, Cornelia Hänel, Heike Busch, Anke Beli, Petra Zarnack, Kathi König, Julian Roignant, Jean-Yves Lasko, Paul PLoS Genet Research Article Makorins are evolutionary conserved proteins that contain C(3)H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR. Public Library of Science 2020-01-24 /pmc/articles/PMC7001992/ /pubmed/31978041 http://dx.doi.org/10.1371/journal.pgen.1008581 Text en © 2020 Dold et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Dold, Annabelle Han, Hong Liu, Niankun Hildebrandt, Andrea Brüggemann, Mirko Rücklé, Cornelia Hänel, Heike Busch, Anke Beli, Petra Zarnack, Kathi König, Julian Roignant, Jean-Yves Lasko, Paul Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title | Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title_full | Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title_fullStr | Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title_full_unstemmed | Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title_short | Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation |
title_sort | makorin 1 controls embryonic patterning by alleviating bruno1-mediated repression of oskar translation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001992/ https://www.ncbi.nlm.nih.gov/pubmed/31978041 http://dx.doi.org/10.1371/journal.pgen.1008581 |
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