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Ribosomal Protein SA (RPSA) is required for localized translation and sarcomere maintenance

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 expression 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 Z-lines. These findings highlight RPSA as a ribosomal factor responsible for ribosome localization to the Z-line, facilitating local translation and sarcomere maintenance.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

SUBMITTER: Tamar Ziv

LAB HEAD: Izhak Kehat

PROVIDER: PXD046385 | Pride | 2024-06-04

REPOSITORIES: Pride

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			Action	DRS
	60851-6txt.rar	Other
	Seq60851_HF.raw	Raw
	Seq60852_HF.raw	Raw
	Seq60853_HF.raw	Raw
	Seq60854_HF.raw	Raw

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