Short stretches of rare codons regulate translation of the transcription factor ZEB2 in cancer cells

Area of Science:

• Molecular Biology
• Developmental Biology
• Cancer Research

Background:

• ZEB1 and ZEB2 are key transcription factors regulating epithelial mesenchymal transition (EMT).
• Understanding the regulation of ZEB protein expression is crucial for developmental processes and cancer progression.

Purpose of the Study:

• To elucidate a novel mechanism controlling ZEB2 protein synthesis.
• To investigate the role of specific protein motifs and codon usage in ZEB2 regulation.

Main Methods:

• Analysis of ZEB2 protein synthesis regulation.
• Identification of a protein motif within the SMAD-binding domain of ZEB2.
• Investigation of rare codon sequences (Leu(UUA)-Gly(GGU)-Val(GUA)) and their impact on translation.
• Comparative analysis with ZEB1 homologous regions.

Main Results:

• A novel mechanism limiting ZEB2 protein synthesis was identified.
• A specific protein motif in ZEB2 induces ribosomal pausing, compromising translation.
• This motif's function depends on rare codon stretches (Leu(UUA)-Gly(GGU)-Val(GUA)).
• Similar codon sequences in ZEB1 did not affect its protein translation.

Conclusions:

• Rare codons can regulate protein synthesis, but their function is context-dependent on protein structure.
• Available transfer RNA pools may influence EMT pathway configurations in tumor cells.