Bicaudal-C spatially controls translation of vertebrate maternal mRNAs.
The Xenopus Cripto-1 protein is confined to the cells of the animal hemisphere during early embryogenesis where it regulates the formation of anterior structures. Cripto-1 protein accumulates only in animal cells because cripto-1 mRNA in cells of the vegetal hemisphere is translationally repressed. Here, we show that the RNA binding protein, Bicaudal-C (Bic-C), functioned directly in this vegetal cell-specific repression. While Bic-C protein is normally confined to vegetal cells, ectopic expression of Bic-C in animal cells repressed a cripto-1 mRNA reporter and associated with endogenous cripto-1 mRNA. Repression by Bic-C required its N-terminal domain, comprised of multiple KH motifs, for specific binding to relevant control elements within the cripto-1 mRNA and a functionally separable C-terminal translation repression domain. Bic-C-mediated repression required the 5' CAP and translation initiation factors, but not a poly(A) tail or the conserved SAM domain within Bic-C. Bic-C-directed immunoprecipitation followed by deep sequencing of associated mRNAs identified multiple Bic-C-regulated mRNA targets, including cripto-1 mRNA, providing new insights and tools for understanding the role of Bic-C in vertebrate development.
Yan
Y
Zhang
Amy
A
Cooke
Sookhee
S
Park
Colin N
CN
Dewey
Marvin
M
Wickens
Michael D
MD
Sheets
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D058851:GPI-Linked Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D023121:RNA, Messenger, Stored / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D029867:Xenopus Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C453440:BICC1 protein, Xenopus; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D023121:RNA, Messenger, Stored; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; C096788:tdgf1.3 protein, Xenopus
Bicaudal-C; Xenopus; maternal mRNAs; translation