A fly trap mechanism provides sequence-specific RNA recognition by CPEB proteins

Area of Science:

• Molecular Biology
• Structural Biology
• RNA Biology

Background:

• Cytoplasmic polyadenylation controls gene expression by altering mRNA poly(A) tail length.
• CPEB proteins bind specific RNA sequences (CPE) in 3' UTRs to regulate translation.
• Dysregulation of CPEB function is linked to various biological processes and diseases.

Purpose of the Study:

• To determine the solution structures of tandem RNA recognition motifs (RRMs) of human CPEB1 and CPEB4.
• To investigate the structural changes upon RNA binding.
• To characterize the role of the ZZ domain in CPEB function.

Main Methods:

• Solution NMR spectroscopy to determine protein structures.
• RNA binding assays.
• Functional characterization of protein domains.

Main Results:

• The structures of free and RNA-bound tandem RRMs of CPEB1 and CPEB4 were solved.
• An unusual RRM arrangement in the free state undergoes a conformational change upon RNA binding for high-fidelity recognition.
• The ZZ domain of CPEB1 is involved in protein-protein and protein-RNA interactions.

Conclusions:

• CPEB protein structures reveal a novel mechanism for RNA-mediated translational control.
• RNA binding induces a conformational change essential for precise target recognition.
• These findings provide insights into the assembly of functional ribonucleoprotein complexes regulating translation.