Chemical Biology
Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16In uveal melanoma tumors, the RNA decay activity of the tumor suppressor miR-16 is impaired by sponge RNAs. These RNAs defined a powerful signature to predict overall survival.
Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferaseThe role of metal ions and specific interactions of dNTP with active-site amino acid residues in the mechanisms underlying the recognition of nucleoside triphosphates by human terminal deoxynucleotidyltransferase were revealed by pre–steady-state kinetics and molecular dynamics approaches.
Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndromeThe authors use photocrosslinking activity-based probes to monitor RNF12/RLIM E3 ubiquitin ligase activity and report the impact of Tonne-Kalscheuer syndrome (TOKAS) patient variants on catalysis.
C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neuronsExtracellularly delivered poly-GAs are internalised into astrocytes via an endocytosis-dependent pathway and then spread to motor neurons, implying non-cell autonomous mechanisms in C9ORF72-ALS/FTD.
Adipose tissue–specific ablation of Ces1d causes metabolic dysregulation in miceCes1d is a crucial enzyme in adipose tissue. Here, we found a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce unique fatty acids which are key for glucose and lipid metabolism.
Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivityThe tumor suppressor protein p53 inhibits ferroptosis by reducing the consumption of glutathione in nucleotide biosynthesis.
USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylationA new inhibitor of the deubiquitylase USP30, an actionable target relevant to Parkinson’s Disease, is introduced and characterised for parameters related to mitophagy.
Caspase-1 interdomain linker cleavage is required for pyroptosisThe related human NLRP1 and CARD8 form ASC-dependent and ASC-independent inflammasomes, respectively, both of which require pro-caspase-1 interdomain linker processing for the induction of pyroptosis.
Phenotypic proteomic profiling identifies a landscape of targets for circadian clock–modulating compoundsThis study provides comprehensive insights into the mechanism of action and cellular effects of circadian period–modulating compounds, which is critical for clearly defining molecular targets to modulate daily rhythms for therapeutic benefit.
Plasmalogen loss caused by remodeling deficiency in mitochondria31P NMR unveils cell type–dependent losses of plasmalogen in the chain remodeling–deficient brain, liver, kidney, and lymphoblast in association with aberrant mitochondrial function and morphology.