A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development

Megan E Dowdle; Sookhee Park; Susanne Blaser Imboden; Catherine A Fox; Douglas W Houston; Michael D Sheets

doi:10.1242/dev.172486

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A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development

Journal article

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Peer reviewed

A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development

Megan E Dowdle, Sookhee Park, Susanne Blaser Imboden, Catherine A Fox, Douglas W Houston and Michael D Sheets

Development (Cambridge), Vol.146(10), p.dev172486

05/15/2019

DOI: 10.1242/dev.172486

PMCID: PMC6550016

PMID: 31023875

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Abstract

Bicaudal-C (Bicc1) is a conserved RNA-binding protein that represses the translation of selected mRNAs to control development. In embryos, Bicc1 binds and represses specific maternal mRNAs to control anterior-posterior cell fates. However, it is not known how Bicc1 binds its RNA targets or how binding affects Bicc1-dependent embryogenesis. Focusing on the KH domains, we analyzed Bicc1 mutants for their ability to bind RNA substrates and Analyses of these Bicc1 mutants demonstrated that a single KH domain, KH2, was crucial for RNA binding and , while the KH1 and KH3 domains contributed minimally. The Bicc1 mutants were also assayed for their ability to repress translation, and results mirrored the RNA-binding data, with KH2 being the only domain essential for repression. Finally, maternal knockdown and rescue experiments indicated that the KH domains were essential for the regulation of embryogenesis by Bicc1. These data advance our understanding of how Bicc1 selects target mRNAs and provide the first direct evidence that the RNA binding functions of Bicc1 are essential for both Bicc1-dependent translational repression and maternal vertebrate development.

RNA-Binding Proteins - genetics

Immunoprecipitation

Xenopus Proteins - genetics

RNA, Messenger - genetics

Xenopus laevis

Embryonic Development - genetics

3' Untranslated Regions - genetics

Embryonic Development - physiology

Immunoblotting

RNA, Messenger - metabolism

Animals

Protein Binding

Female

Xenopus Proteins - metabolism

3' Untranslated Regions - physiology

RNA-Binding Proteins - metabolism

Details

Title: Subtitle: A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development
Creators: Megan E Dowdle - Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
Sookhee Park - Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
Susanne Blaser Imboden - Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
Catherine A Fox - Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
Douglas W Houston - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
Michael D Sheets - Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA mdsheets@wisc.edu
Resource Type: Journal article
Publication Details: Development (Cambridge), Vol.146(10), p.dev172486
Publisher: England
DOI: 10.1242/dev.172486
PMID: 31023875
PMCID: PMC6550016
ISSN: 1477-9129
eISSN: 1477-9129
Grant note: R01 GM083999 / NIGMS NIH HHS T32 GM008349 / NIGMS NIH HHS R01 HD091921 / NICHD NIH HHS R01 GM056890 / NIGMS NIH HHS R21 HD076828 / NICHD NIH HHS
Language: English
Date published: 05/15/2019
Academic Unit: Biology
Record Identifier: 9983991957702771

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