Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.

A complex program of translational repression, mRNA localization, and translational activation ensures that Oskar (Osk) protein accumulates only at the posterior pole of the Drosophila oocyte. Inappropriate expression of Osk disrupts embryonic axial patterning, and is lethal. A key factor in transla...

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Main Authors: Goheun Kim, Chin-I Pai, Keiji Sato, Maria D Person, Akira Nakamura, Paul M Macdonald
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC4344327?pdf=render
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spelling doaj-a962f35f10354c40b2a43d443ede0b7e2020-11-24T21:42:00ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-01-01112e100499210.1371/journal.pgen.1004992Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.Goheun KimChin-I PaiKeiji SatoMaria D PersonAkira NakamuraPaul M MacdonaldA complex program of translational repression, mRNA localization, and translational activation ensures that Oskar (Osk) protein accumulates only at the posterior pole of the Drosophila oocyte. Inappropriate expression of Osk disrupts embryonic axial patterning, and is lethal. A key factor in translational repression is Bruno (Bru), which binds to regulatory elements in the osk mRNA 3' UTR. After posterior localization of osk mRNA, repression by Bru must be alleviated. Here we describe an in vivo assay system to monitor the spatial pattern of Bru-dependent repression, separate from the full complexity of osk regulation. This assay reveals a form of translational activation-region-specific activation-which acts regionally in the oocyte, is not mechanistically coupled to mRNA localization, and functions by inhibiting repression by Bru. We also show that Bru dimerizes and identify mutations that disrupt this interaction to test its role in vivo. Loss of dimerization does not disrupt repression, as might have been expected from an existing model for the mechanism of repression. However, loss of dimerization does impair regional activation of translation, suggesting that dimerization may constrain, not promote, repression. Our work provides new insight into the question of how localized mRNAs become translationally active, showing that repression of osk mRNA is locally inactivated by a mechanism acting independent of mRNA localization.http://europepmc.org/articles/PMC4344327?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Goheun Kim
Chin-I Pai
Keiji Sato
Maria D Person
Akira Nakamura
Paul M Macdonald
spellingShingle Goheun Kim
Chin-I Pai
Keiji Sato
Maria D Person
Akira Nakamura
Paul M Macdonald
Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
PLoS Genetics
author_facet Goheun Kim
Chin-I Pai
Keiji Sato
Maria D Person
Akira Nakamura
Paul M Macdonald
author_sort Goheun Kim
title Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
title_short Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
title_full Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
title_fullStr Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
title_full_unstemmed Region-specific activation of oskar mRNA translation by inhibition of Bruno-mediated repression.
title_sort region-specific activation of oskar mrna translation by inhibition of bruno-mediated repression.
publisher Public Library of Science (PLoS)
series PLoS Genetics
issn 1553-7390
1553-7404
publishDate 2015-01-01
description A complex program of translational repression, mRNA localization, and translational activation ensures that Oskar (Osk) protein accumulates only at the posterior pole of the Drosophila oocyte. Inappropriate expression of Osk disrupts embryonic axial patterning, and is lethal. A key factor in translational repression is Bruno (Bru), which binds to regulatory elements in the osk mRNA 3' UTR. After posterior localization of osk mRNA, repression by Bru must be alleviated. Here we describe an in vivo assay system to monitor the spatial pattern of Bru-dependent repression, separate from the full complexity of osk regulation. This assay reveals a form of translational activation-region-specific activation-which acts regionally in the oocyte, is not mechanistically coupled to mRNA localization, and functions by inhibiting repression by Bru. We also show that Bru dimerizes and identify mutations that disrupt this interaction to test its role in vivo. Loss of dimerization does not disrupt repression, as might have been expected from an existing model for the mechanism of repression. However, loss of dimerization does impair regional activation of translation, suggesting that dimerization may constrain, not promote, repression. Our work provides new insight into the question of how localized mRNAs become translationally active, showing that repression of osk mRNA is locally inactivated by a mechanism acting independent of mRNA localization.
url http://europepmc.org/articles/PMC4344327?pdf=render
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