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Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence.


ABSTRACT: ?- and ?-cytoplasmic actin are nearly indistinguishable in their amino acid sequence, but are encoded by different genes that play non-redundant biological roles. The key determinants that drive their functional distinction are unknown. Here, we tested the hypothesis that ?- and ?-actin functions are defined by their nucleotide, rather than their amino acid sequence, using targeted editing of the mouse genome. Although previous studies have shown that disruption of ?-actin gene critically impacts cell migration and mouse embryogenesis, we demonstrate here that generation of a mouse lacking ?-actin protein by editing ?-actin gene to encode ?-actin protein, and vice versa, does not affect cell migration and/or organism survival. Our data suggest that the essential in vivo function of ?-actin is provided by the gene sequence independent of the encoded protein isoform. We propose that this regulation constitutes a global 'silent code' mechanism that controls the functional diversity of protein isoforms.

SUBMITTER: Vedula P 

PROVIDER: S-EPMC5794254 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence.

Vedula Pavan P   Kurosaka Satoshi S   Leu Nicolae Adrian NA   Wolf Yuri I YI   Shabalina Svetlana A SA   Wang Junling J   Sterling Stephanie S   Dong Dawei W DW   Kashina Anna A  

eLife 20171215


β- and γ-cytoplasmic actin are nearly indistinguishable in their amino acid sequence, but are encoded by different genes that play non-redundant biological roles. The key determinants that drive their functional distinction are unknown. Here, we tested the hypothesis that β- and γ-actin functions are defined by their nucleotide, rather than their amino acid sequence, using targeted editing of the mouse genome. Although previous studies have shown that disruption of β-actin gene critically impact  ...[more]

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