Determinants of RNA Binding and Translational Repression by the Bicaudal-C Regulatory Protein

作者：Zhang Yan; Park Sookhee; Blaser Susanne; Sheets Michael D^*

来源：Journal of Biological Chemistry, 2014, 289(11): 7497-7504.

DOI：10.1074/jbc.M113.526426

• Development
• Kidney
• mRNA
• RNA Binding Protein
• RNA Silencing
• Transforming Growth Factor Beta (TGFbeta)
• Translation Regulation
• Xenopus
• Maternal mRNA

Background: Bicaudal-C RNA binding proteins are important translational repressors in many different biological contexts. Results: A minimal site for RNA binding and translation repression by Bicaudal-C was identified. Conclusion: The RNA binding site for Bicaudal-C forms a stem-loop structure important for binding and translational repression. Significance: This will facilitate the identification of Bicaudal-C binding sites in other mRNAs.
Bicaudal-C (Bic-C) RNA binding proteins function as important translational repressors in multiple biological contexts within metazoans. However, their RNA binding sites are unknown. We recently demonstrated that Bic-C functions in spatially regulated translational repression of the xCR1 mRNA during Xenopus development. This repression contributes to normal development by confining the xCR1 protein, a regulator of key signaling pathways, to specific cells of the embryo. In this report, we combined biochemical approaches with in vivo mRNA reporter assays to define the minimal Bic-C target site within the xCR1 mRNA. This 32-nucleotide Bic-C target site is predicted to fold into a stem-loop secondary structure. Mutational analyses provided evidence that this stem-loop structure is important for Bic-C binding. The Bic-C target site was sufficient for Bic-C mediated repression in vivo. Thus, we describe the first RNA binding site for a Bic-C protein. This identification provides an important step toward understanding the mechanisms by which evolutionarily conserved Bic-C proteins control cellular function in metazoans.

• 出版日期2014-3-14