Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.07.26.550187v1?rss=1
Authors: Sadeh, O., Haddad, R., Ziv, T., Haimovich-Caspi, L., Shemesh, A., Kehat, I.
Abstract:
Cardiomyocyte sarcomeres contain localized ribosomes, but the factors responsible for their localization and the significance of localized translation are unknown. Using proximity labeling, we identified Ribosomal Protein SA (RPSA) as a Z-line protein. In cultured cardiomyocytes, the loss of RPSA led to impaired local protein translation and reduced sarcomere integrity. By employing CAS9 expressing mice along with adeno-associated viruses expressing CRE recombinase and single-guide RNAs targeting Rpsa, we knocked out RPSA in vivo and observed mis-localization of ribosomes and diminished local translation. These genetic mosaic mice with RPSA knockout in a subset of cardiomyocytes developed dilated cardiomyopathy, featuring atrophy of RPSA-deficient cardiomyocytes, compensatory hypertrophy of unaffected cardiomyocytes, left ventricular dilation, and impaired contractile function. We demonstrate that RPSA C-terminal domain is sufficient for localization to the Z-lines. These findings highlight RPSA as a ribosomal factor responsible for ribosome localization to the Z-line, facilitating local translation and sarcomere maintenance.
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