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bioRxiv · 10.1101/227546

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

Vedula, P.·Kurosaka, S.·Leu, N.·Wolf, Y.·Shabalina, S.·Wang, J.·Sterling, S.·Dong, D.·Kashina, A.
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Abstract

{beta}- and {gamma}-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 {beta}- and {gamma}-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 {beta}-actin gene critically impacts cell migration and mouse embryogenesis, we demonstrate here that generation of a mouse lacking {beta}-actin protein by editing {beta}-actin gene to encode {gamma}-actin protein, and vice versa, does not affect cell migration and/or organism survival. Our data suggest that the essential in vivo function of {beta}-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.

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Vedula, P., Kurosaka, S., Leu, N., Wolf, Y., Shabalina, S., Wang, J., Sterling, S., Dong, D., Kashina, A.. 2017-12-01. Diverse functions of closely homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence.. https://doi.org/10.1101/227546

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