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mt-tRNAs in the polymerase gamma mutant heart.
Bayazit, M Bilal; Francois, Ashley; McGrail, Erin; Accornero, Federica; Stratton, Matthew S.
Afiliación
  • Bayazit MB; Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Francois A; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
  • McGrail E; Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Accornero F; Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
  • Stratton MS; Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
J Cardiovasc Aging ; 3(4)2023 Oct.
Article en En | MEDLINE | ID: mdl-38235059
ABSTRACT

Introduction:

Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPTmt) - like (UPRmt-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice.

Aim:

We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress. Methods and

Results:

The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid's amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data.

Conclusion:

We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid's amyloidogenic properties.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Aging Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Aging Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos