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

• Published in: Development (Cambridge) Vol. 146; no. 10
• Main Authors: Dowdle, Megan E, Park, Sookhee, Blaser Imboden, Susanne, Fox, Catherine A, Houston, Douglas W, Sheets, Michael D
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15-05-2019
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - physiology; Animals; Embryonic Development - genetics; Embryonic Development - physiology; Female; Immunoblotting; Immunoprecipitation; Protein Binding; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Xenopus laevis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Maternal; Bicaudal-C; Post-transcriptional; mRNA translation; Repression; RNA binding
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.172486

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.