Reovirus μ2 Protein Impairs Translation to Reduce U5 snRNP Protein Levels

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Mammalian orthoreovirus (MRV) infects mammals and alters cellular alternative splicing (AS).
• The viral protein μ2 is implicated in AS modifications by reducing U5 core components.

Purpose of the Study:

• To investigate the mechanism by which MRV protein μ2 affects U5 snRNP components.
• To elucidate how MRV alters cellular alternative splicing.

Main Methods:

• Investigated effects of μ2 on mRNA levels, RNA export, and protein stability.
• Utilized polysome profiling and metabolic labeling to assess translation.
• Examined localization effects using μ2 mutants.
• Performed co-expression experiments to determine dose-dependency.

Main Results:

• μ2 does not affect steady-state mRNA levels, RNA export, or protein stability of U5 snRNP proteins.
• μ2 inhibits global translation and reduces U5 snRNP component levels, primarily in the cytoplasm.
• μ2 suppresses U5 snRNP protein expression in a dose-dependent manner with varying sensitivities.

Conclusions:

• MRV protein μ2 reduces U5 core components via translation inhibition.
• This novel mechanism enables viral alteration of cellular alternative splicing during infection.