Keeping it fresh: ribosomal protein SA sustains sarcomeric function via localized translation

J Clin Invest. 2024 Jul 1;134(13):e181996. doi: 10.1172/JCI181996.

Abstract

Mechanical stress from cardiomyocyte contraction causes misfolded sarcomeric protein replacement. Sarcomeric maintenance utilizes localized pools of mRNAs and translation machinery, yet the importance of localized translation remains unclear. In this issue of the JCI, Haddad et al. identify the Z-line as a critical site for localized translation of sarcomeric proteins, mediated by ribosomal protein SA (RPSA). RPSA localized ribosomes at Z-lines and was trafficked via microtubules. Cardiomyocyte-specific loss of RPSA in mice resulted in mislocalized protein translation and caused structural dilation from myocyte atrophy. These findings demonstrate the necessity of RPSA-dependent spatially localized translation for sarcomere maintenance and cardiac structure and function.

MeSH terms

  • Animals
  • Humans
  • Mice
  • Microtubules / metabolism
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • Protein Biosynthesis*
  • Ribosomal Proteins* / genetics
  • Ribosomal Proteins* / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Sarcomeres* / metabolism
  • Sarcomeres* / pathology

Substances

  • Ribosomal Proteins