Tau drives translational selectivity by interacting with ribosomal proteins

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Tau protein aggregation is a hallmark of neurodegenerative diseases.
• Tau's interaction with ribosomes and its effect on protein synthesis are not well understood.
• Ribosome function is critical for cellular health and neuronal function.

Purpose of the Study:

• To investigate the consequences of tau-ribosome interactions.
• To determine if tau modulates ribosomal selectivity and protein synthesis.
• To link aberrant tau-ribosome interactions to cognitive impairment in tauopathies.

Main Methods:

• Utilized transgenic mouse models (rTg4510) with regulatable tau expression.
• Performed microarrays and nascent proteomics to analyze changes in protein synthesis.
• Examined tau interactions with ribosomes in cell cultures and human brain tissues.

Main Results:

• Tau expression alters the transcriptome and nascent proteome, affecting ribosomal protein synthesis.
• Tau pathologically interacts with ribosomal protein S6 (rpS6), a translation regulator.
• Protein synthesis regulated by rpS6 is reduced in tauopathic conditions and Alzheimer's disease brains.

Conclusions:

• Tau is identified as a direct modulator of ribosomal selectivity and RNA translation.
• Aberrant tau-ribosome interactions disrupt protein synthesis, potentially explaining cognitive deficits in tauopathies.
• This study establishes a mechanistic link between tau pathology and impaired protein synthesis regulation.