Volume 26 Issue 7, July 2024

Aminoacyl-tRNA synthetases can promote or suppress cancer progression by regulating codon-dependent translation. A study now shows that valine aminoacyl-tRNA synthetase (VARS) promotes therapeutic resistance of melanoma to MAPK pathway inhibitors by enhancing translation of valine-enriched genes, including the fatty acid oxidation gene HADH.

R-loops and G-quadruplexes are non-canonical nucleic acid structures with known roles in genome organization. Here, Wulfridge and Sarma highlight emerging roles in DNA repair and transcriptional and epigenetic gene regulation.

The subcellular localization of numerous mRNAs has been demonstrated. This Review presents the different means of mRNA localization described and discusses how they can account for the widespread occurrence of this phenomenon.

Jungnickel, Guelle et al. use metabolomics, electrophysiology and cryo-EM approaches to show that MFSD1 is a lysosomal dipeptide uniporter, which provides an additional route to recycle lysosomal proteolysis products to lysosomal amino acid exporters.

Lin, Pal, et al. report a role for localized activation of Ras activity in promoting cell polarity and motility.

Sun, Tao, Han et al. identify the Rabs involved in unconventional protein secretion mediated by TMED10 and in ER–Golgi intermediate compartment organization.

Palmulli, Couty and colleagues show that the tetraspanin CD63 promotes accumulation of cholesterol in intraluminal vesicles (ILVs) at the expense of retrieval from endosomes; cholesterol stored in ILVs and exosomes is recovered in an NPC1-dependent manner.

Jiang et al. document an abundance of neutrophil-derived migrasomes in the blood of mice and humans and show that migrasomes are enriched in coagulation factors, accumulate at sites of injury and trigger platelet activation and clot formation.

Harasimov, Gorry, Welp, Penir, Horokhovskyi et al. analyse proteostasis in mammalian oocytes and ovaries: the maintenance of oocytes involves exceptional protein longevity, and many of the extremely long-lived proteins decline as the ovary ages.

Zhang and Seemann show that GM130 forms a complex with RNA-binding proteins. RNA binding of GM130 induces liquid–liquid phase separation and these co-condensates function to link the Golgi ribbon.

El-Hachem et al. show that MAPK therapy upregulates valine aminoacyl-tRNA synthetase and alters fatty acid oxidation by promoting translation of valine-enriched transcripts, providing a resistance mechanism that may be therapeutically targeted.

Seehawer et al. show that deletion of Kmt2c or Kmt2d promotes brain metastasis in mouse models of triple-negative breast cancer due to altered KDM6A activity and upregulated MMP3 expression, which may constitute a potential therapeutic target.

With ultra-deep RNA sequencing, Zhang et al. report increased usage of alternative promoters driven by AR, FOXA1 and MYC during prostate cancer progression and suggest altered DNA methylation as a potential underlying mechanism.

In two independent studies, Sun, Liu et al. and Sun et al. develop SPATAC-seq to map the chromatin accessibility landscape of zebrafish embryogenesis and mouse organogenesis, respectively, and identify transcription regulators that determine cell fate.

In two independent studies, Sun, Liu et al. and Sun et al. develop SPATAC-seq to map the chromatin accessibility landscape of zebrafish embryogenesis and mouse organogenesis, respectively, and identify transcription regulators that determine cell fate.

Qin, Liu and colleagues develop a tool that combines CRISPR technology with G-quadruplex (G4)-stabilizing protein or ligand to specifically target DNA G4 structures. This tool provides better understanding of G4 functions and enables G4-based drug development.