A paradigm for regulation at the effector interface with RNA-binding proteins.

Area of Science:

• Molecular Biology
• Gene Regulation

Background:

• RNA-binding proteins (RBPs) regulate gene expression, but the mechanisms by which they interact with RNA processing effectors are not fully understood.
• The precise nature of RBP-effector interfaces remains a key question in understanding gene regulation networks.

Approach:

• Investigated the Unkempt RBP, a conserved protein crucial for metazoan development, to elucidate its effector interface.
• Characterized novel 'dual-purpose' peptide motifs mediating multivalent contacts within the RBP-effector interface.
• Utilized systems analyses to explore the functional consequences of these multivalent interactions, including effector repurposing.

Key Points:

• A multivalent RBP-effector interface, mediated by novel dual-purpose peptide motifs, has been identified in the Unkempt protein.
• These multivalent contacts are essential for accurate RNA recognition by the RBP, not just effector recruitment.
• The study demonstrates the repurposing of the CCR4-NOT mRNA decay factor for translational control via these RBP-effector interactions.

Conclusions:

• Established the molecular assembly and functional principles of a novel RBP-effector interface.
• Highlighted the role of multivalent interactions in enhancing RNA recognition accuracy and enabling functional repurposing of effectors.
• Provided insights into the evolution and function of RBP-operated regulatory networks in gene expression.