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An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis

ABSTRACT: An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis

PROVIDER: PRJNA415988 | ENA |

REPOSITORIES: ENA

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An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis

2018-03-01 | GSE106246 | GEO

Ribosome profiling and RNA-Sequencing of wild type and Pelota knockout mouse epidermis

Project description:mRNA quality control mechanisms ensure fidelity of protein translation. An evolutionarily conserved component of the quality control machinery, Dom34/Pelota (Pelo), rescues stalled ribosomes. Here we show that Pelo is required for mammalian epidermal homeostasis. Conditional deletion in murine epidermal stem cells expressing Lrig1 results in hyperproliferation and abnormal differentiation, whereas deletion in other stem cells does not. Loss of Pelo results in truncated ribosome footprints and global upregulation of translation. Translational inhibition by rapamycin-mediated down regulation of mTOR rescues the epidermal phenotype. Our study reveals a novel role for the ribosome-rescue machinery in mammalian tissue homeostasis and an unanticipated specificity in its impact on different stem cell populations.

2017-02-02 | GSE94385 | GEO

Ribosome collisions in bacteria promote ribosome rescue by triggering mRNA cleavage by SmrB

Project description:Ribosome rescue pathways recycle stalled ribosomes and target problematic mRNAs and aborted proteins for degradation. In bacteria, it remains unclear how rescue pathways distinguish ribosomes stalled in the middle of a transcript from actively translating ribosomes. In a genetic screen in E. coli, we discovered a novel rescue factor that has endonuclease activity. SmrB cleaves mRNAs upstream of stalled ribosomes, allowing the ribosome rescue factor tmRNA (which acts on truncated mRNA) to rescue upstream ribosomes. SmrB is recruited by ribosome collisions. Cryo-EM structures of collided disomes from E. coli and B. subtilis reveal interactions between the 30S subunits and a possible SmrB binding site. These findings show that ribosome collisions trigger ribosome rescue in bacteria and reveal the mechanism by which this occurs.

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The evolutionarily conserved zebrafish choroid plexus maintains the size of brain ventricles

Project description:The choroid plexus produces cerebrospinal fluid (CSF) by transport of electrolytes and water from the vasculature to the brain ventricles. The choroid plexus plays additional roles in brain development and homeostasis by secreting neurotrophic molecules, and by serving as a CSF-blood barrier and immune interface. Prior studies have identified transporters on the epithelial cells that transport water and ions into the ventricles and tight junctions involved in the CSF-blood barrier. Yet, how the choroid plexus epithelial cells maintain the brain ventricle system and control brain physiology remain unresolved. To provide novel insights into the physiological roles of the choroid plexus, we use juvenile and adult zebrafish as model systems. Upon histological and transcriptomic analyses, we first identified that the zebrafish choroid plexus is highly conserved with the mammalian choroid plexus and that it expresses all transporters necessary for CSF secretion. Using novel genetic lines, we also identified that the choroid plexus secretes proteins into the CSF. Next, we generated a transgenic line allowing us to ablate specifically the epithelial cells in the choroid plexus. Using the ablation system, we identified a reduction of the ventricular sizes, but no alterations of the CSF-blood barrier. Altogether, our findings identified that the zebrafish choroid plexus is evolutionarily conserved and critical for maintaining the size and homeostasis of the brain ventricles.

2024-05-06 | GSE246851 | GEO

A transphyletic approach to analyzing evolutionarily conserved β-catenin modules

Project description:To identify evolutionarily conserved Beta-catenin protein interactions, Beta-catenin mRNA from various metazoans was injected into Xenopus embryos and immunopurified at gastrula stage. Beta-catenin complexes were then separated on an SDS-PAGE gel and subjected mass spectrometric analysis

2023-07-08 | PXD035167 | JPOST Repository