A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma.

http://www.cell.com/article/S221112472200417X/pdf

Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

The proteasome is responsible for selective degradation of most cellular proteins. Abundantly present in the cell, proteasomes not only diffuse in the cytoplasm and the nucleus but also associate with the chromatin, cytoskeleton, various membranes and membraneless organelles/condensates. How and why the proteasome gets to these specific subcellular compartments remains poorly understood, although increasing evidence supports the hypothesis that intracellular localization may have profound impacts on the activity, substrate accessibility and stability/integrity of the proteasome. In this short review, I summarize recent advances on the functions, regulations and targeting mechanisms of proteasomes, especially those localized to the nuclear condensates and membrane structures of the cell, and I discuss the biological significance thereof in mediating compartmentalized protein degradation.

/pdf/localized-proteasomal-degradation-from-the-nucleus-to-cell-27w4jtvf.pdf

Localized Proteasomal Degradation: From the Nucleus to Cell Periphery

Mistranslation, the misincorporation of an amino acid not specified by the "standard" genetic code, occurs in all organisms. tRNA variants that increase mistranslation arise spontaneously and engineered tRNAs can achieve mistranslation frequencies approaching 10% in yeast and bacteria. Interestingly, human genomes contain tRNA variants with the potential to mistranslate. Cells cope with increased mistranslation through multiple mechanisms, though high levels cause proteotoxic stress. The goal of this study was to compare the genetic interactions and the impact on transcriptome and cellular growth of two tRNA variants that mistranslate at a similar frequency but create different amino acid substitutions in Saccharomyces cerevisiae. One tRNA variant inserts alanine at proline codons whereas the other inserts serine for arginine. Both tRNAs decreased growth rate, with the effect being greater for arginine to serine than for proline to alanine. The tRNA that substituted serine for arginine resulted in a heat shock response. In contrast, heat shock response was minimal for proline to alanine substitution. Further demonstrating the significance of the amino acid substitution, transcriptome analysis identified unique up- and down-regulated genes in response to each mistranslating tRNA. Number and extent of negative synthetic genetic interactions also differed depending upon type of mistranslation. Based on the unique responses observed for these mistranslating tRNAs, we predict that the potential of mistranslation to exacerbate diseases caused by proteotoxic stress depends on the tRNA variant. Furthermore, based on their unique transcriptomes and genetic interactions, different naturally occurring mistranslating tRNAs have the potential to negatively influence specific diseases.

The amino acid substitution affects cellular response to mistranslation.

Determining and interpreting protein lifetimes in mammalian tissues.

Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network

The hydrophobic nature of a material is determined by both its surface chemistry and its physical structure. In order to unravel the factors underpinning the OHM sponge’s unusual hydrophobic nature, we characterized the unique interfaces of this composite material in the context of solid-fluid interactions using a correlative approach. Here we apply a combination of SEM, TEM and Raman spectroscopy to probe the structure, morphology and chemistry of the sponge at multiple length scales. This correlative and multimodal approach is fundamental to fully depict the structure-property relationship of the OHM sponge and overcome the intrinsic challenges of studying hard-soft interfaces. [3-5]

/pdf/multimodal-characterization-of-the-oleophilic-hydrophobic-2z9o103nc4.pdf

Tirzah Abbott

Papers

Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network

Multimodal Characterization of the Oleophilic Hydrophobic Magnetic (OHM) Sponge: A Nanocomposite Material for Oil Spill Remediation

Search for the Carriers of P-process Anomalies in Early Solar System Condensates

Exploring the inner space of outer space: multi-length scale, multimodal characterization of Muonionalusta IVA iron meteorite