A humanized NOVA1 splicing factor alters mouse vocal communications

Tajima, Yoko, Vargas, César DM, Ito, Keiichi, Wang, Wei, Luo, Ji-Dung, Xing, Jiawei, Kuru, Nurdan, Machado, Luiz Carlos, Siepel, Adam, Carroll, Thomas S, Jarvis, Erich D, Darnell, Robert B (February 2025) A humanized NOVA1 splicing factor alters mouse vocal communications. Nature Communications, 16 (1). p. 1542. ISSN 2041-1723 (Public Dataset)

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Abstract

NOVA1, a neuronal RNA-binding protein expressed in the central nervous system, is essential for survival in mice and normal development in humans. A single amino acid change (I197V) in NOVA1's second RNA binding domain is unique to modern humans. To study its physiological effects, we generated mice carrying the human-specific I197V variant (Nova1hu/hu) and analyzed the molecular and behavioral consequences. While the I197V substitution had minimal impact on NOVA1's RNA binding capacity, it led to specific effects on alternative splicing, and CLIP revealed multiple binding peaks in mouse brain transcripts involved in vocalization. These molecular findings were associated with behavioral differences in vocalization patterns in Nova1hu/hu mice as pups and adults. Our findings suggest that this human-specific NOVA1 substitution may have been part of an ancient evolutionary selective sweep in a common ancestral population of Homo sapiens, possibly contributing to the development of spoken language through differential RNA regulation during brain development.

Item Type: Paper
Subjects: organism description > animal
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
organism description > animal > mammal > rodent
CSHL Authors:
Communities: CSHL labs > Siepel lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 18 February 2025
Date Deposited: 19 Feb 2025 13:39
Last Modified: 19 Feb 2025 13:39
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/41798

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