Beta- and  Gamma-cytoplasmic  actin  are  nearly indistinguishable in
   their amino acid sequence, but are  encoded  by  different genes that
   play nonredundant 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.

   (eLife, 6:e31661, doi:10.7554/eLife.31661, 2017)