A humanized NOVA1 splicing factor alters mouse vocal communications.

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genetics

Background:

• NOVA1 is a crucial neuronal RNA-binding protein for survival and development.
• A human-specific amino acid substitution (I197V) exists in NOVA1's RNA binding domain.

Purpose of the Study:

• To investigate the physiological effects of the human-specific NOVA1 I197V variant.
• To analyze the molecular and behavioral consequences of this variant in a mouse model.

Main Methods:

• Generated mice with the human-specific I197V variant (Nova1^hu/hu).
• Assessed RNA binding capacity, alternative splicing, and RNA-protein interactions (CLIP).
• Analyzed vocalization patterns in Nova1^hu/hu mice.

Main Results:

• The I197V substitution minimally affected NOVA1 RNA binding.
• Specific alterations in alternative splicing were observed.
• CLIP identified binding sites in vocalization-related transcripts.
• Nova1^hu/hu mice exhibited distinct vocalization patterns.

Conclusions:

• The human-specific NOVA1 I197V variant influences alternative splicing and vocalization.
• This variant may have undergone positive selection in human evolution.
• It could have contributed to the development of spoken language via RNA regulation in brain development.