The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain DOI Creative Commons
Lauryn Higginson, Xingjun Wang, Kevin He

et al.

Published: Oct. 30, 2024

Abstract Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate levels. Inherited mutations genes encoding ubiquitous RNases associated with human diseases, primarily affecting the nervous system. Recessive an evolutionarily conserved RNase complex, exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b). We establish a CRISPR/Cas9-engineered Drosophila model PCH1b study cell-type-specific post-transcriptional regulatory functions nuclear exosome complex within fly head tissue. Here, we report that pathogenic alter activity causing widespread dysregulation brain-enriched cellular transcriptomes, rRNA processing defects—resulting tissue-specific, neurodegenerative effects flies. These findings provide comprehensive understanding function developed animal brain and underscore critical role machinery homeostasis brain.

Language: Английский

Built differently or defective: can RNA exosomopathies cause ribosome heterogeneity? DOI Creative Commons

Zachary J. Bressman,

Anita H. Corbett, Homa Ghalei

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2025, Volume and Issue: 380(1921)

Published: March 6, 2025

The RNA exosome is an essential, evolutionarily conserved ribonuclease required for processing and degradation of key cellular RNAs. complex maintains homeostasis within every cell by ensuring the proper maturation, quality control turnover various species including rRNAs. A growing list diseases, collectively termed exosomopathies, are caused mutations in genes encoding structural subunits complex. exosomopathies often result tissue-specific defects, particularly manifesting as neurological disorders, which intriguing given ubiquitous functions expression exosome. One such ubiquitous, essential function its involvement ribosome biogenesis. In this review, we discuss established connections between biogenesis, exploring potential mechanisms through could influence heterogeneity, leading to aberrant translation pathogenesis. We highlight critical need research area that can aid understanding aetiology future development therapeutic strategies mitigate pathology.This article part discussion meeting issue 'Ribosome diversity impact on protein synthesis, disease'.

Language: Английский

Citations

0
The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain DOI Creative Commons
Lauryn Higginson, Xingjun Wang, Kevin He

et al.

Published: Oct. 30, 2024

Abstract Intracellular ribonucleases (RNases) are essential in all aspects of RNA metabolism, including maintaining accurate levels. Inherited mutations genes encoding ubiquitous RNases associated with human diseases, primarily affecting the nervous system. Recessive an evolutionarily conserved RNase complex, exosome, lead to syndromic neurodevelopmental disorders characterized by progressive neurodegeneration, such as Pontocerebellar Hypoplasia Type 1b (PCH1b). We establish a CRISPR/Cas9-engineered Drosophila model PCH1b study cell-type-specific post-transcriptional regulatory functions nuclear exosome complex within fly head tissue. Here, we report that pathogenic alter activity causing widespread dysregulation brain-enriched cellular transcriptomes, rRNA processing defects—resulting tissue-specific, neurodegenerative effects flies. These findings provide comprehensive understanding function developed animal brain and underscore critical role machinery homeostasis brain.

Language: Английский

Citations

0