Disruption of tRNA biogenesis enhances proteostatic resilience, improves later-life health, and promotes longevity.

tRNAs are evolutionarily ancient molecular decoders essential for protein translation. In eukaryotes, tRNAs and other short, noncoding RNAs are transcribed by RNA polymerase (Pol) III, an enzyme that promotes ageing in yeast, worms, and flies. Here, we show that a partial reduction in Pol III activity specifically disrupts tRNA levels.

Corrigendum: RNA Polymerase III, Ageing and Longevity.

[This corrects the article DOI: 10.3389/fgene.2021.

RNA Polymerase III, Ageing and Longevity.

Transcription in eukaryotic cells is performed by three RNA polymerases. RNA polymerase I synthesises most rRNAs, whilst RNA polymerase II transcribes all mRNAs and many non-coding RNAs. The largest of the three polymerases is RNA polymerase III (Pol III) which transcribes a variety of short non-coding RNAs including tRNAs and the 5S rRNA, in addition to other small RNAs such as snRNAs, snoRNAs, SINEs, 7SL RNA, Y RNA, and U6 spilceosomal RNA.

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage .

Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity.

Probing the unfolded protein response in long-lived naked mole-rats.

The long-living naked mole-rat (NMR) shows negligible senescence and resistance to age-associated diseases. Recent evidence, based on protein-level assays, suggests that enhanced protein homeostasis machinery contributes to NMR stress-resistance and longevity. Here, we develop NMR-specific, transcriptional assays for measuring the unfolded protein response (UPR), a component of ER proteostasis.

The material properties of naked mole-rat hyaluronan.

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells.

MST1/2 Kinase Assays Using Recombinant Proteins.

The Hippo tumor suppressor pathway is fundamental to the coordination of death, growth, proliferation, and differentiation on the cellular level. At the molecular level, a highly conserved Hippo core cassette is central for the regulation of effector activities such as the co-transcriptional activity of YAP. In particular, the mammalian MST1/2 serine/threonine protein kinases (termed Hippo kinase in Drosophila melanogaster) can act as central signal transducers as part of the Hippo core cassette.

A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.

Hippo-like pathways are ancient signaling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase, and non-catalytic protein scaffolds.

Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction.

The characterisation of LATS2 kinase regulation in Hippo-YAP signalling.

By controlling the YAP1 proto-oncoprotein Hippo signalling plays important roles in cancer-associated processes. Current evidence suggests that the Hippo kinases MST1/2 together with the MOB1 scaffold protein promote the formation of active MOB1/LATS complexes which phosphorylate and thereby inhibit YAP1. However, the regulatory mechanisms of MST1/2-MOB1-LATS signalling are currently underinvestigated.

Insoluble protein purification with sarkosyl: facts and precautions.

When eukaryotic proteins are overexpressed in Escherichia coli hosts, they often form inclusion bodies. Natively folded proteins can be extracted from inclusion bodies using mild detergents such as sarkosyl. One common problem is the sequestration of nucleic acid contaminants with the protein of interest.