Volume 25 Issue 4, April 2023

Biomolecular condensation of macromolecules is an increasingly important concept in cell biology. Indeed, research on condensates touches on multiple areas of research, from biochemistry to biophysics and from organelles to cell polarity. We asked experts at the forefront of this field to comment on what excites them most regarding biomolecular condensation, as well as on current challenges, priorities and needs for the functional study of condensates.

DNMT3A is best known for its de novo DNA methyltransferase activity. But a new study shows that the protein also has a role in RNA splicing during activation of embryonic and haematopoietic stem cells. This introduces a new perspective for approaching diseases associated with DNMT3A mutations.

In adult Drosophila, the sense of touch is mediated by mechanosensory organs, namely tactile bristles in the epidermis. A new study reveals that a previously unknown type of epidermal cell, named the F-cell, is recruited to ensheath the tactile bristle and is required for touch sensing.

The house-keeping aminoacyl-tRNA synthetases are increasingly recognized for their regulatory roles beyond protein synthesis. Research now uncovers a function of nuclear arginyl-tRNA synthetase in the regulation of alternative mRNA splicing through SRRM2 in response to inflammation and decreased arginine levels.

The molecular and cellular events that occur during the onset of human organogenesis remain mysterious. We used single-cell and spatial transcriptomics to provide a global view of human embryonic cell-type specification, shedding light on developmental processes such as axial patterning, stage transition, and differences between human and mouse embryonic development.

Using single-cell transcriptomics and functional assays, we identified various subsets of pancreatic beta cells. One subset, characterized by high levels of CD63, demonstrated enhanced glucose metabolism, mitochondrial activity, and glucose-induced insulin secretion, and the proportion of these beta cells was decreased in mouse models of type 2 diabetes (T2D) and humans with T2D.

We discovered that SARS-CoV-2 infection causes DNA damage both in cultured cells and in vivo. Mechanistically, SARS-CoV-2 degrades the enzyme CHK1, which leads to a reduction in dNTPs and impaired DNA replication. Moreover, inhibition of the formation of binding protein 53BP1 foci by the SARS-CoV-2 nucleocapsid protein hinders the repair of damaged DNA. The ensuing accumulation of DNA damage causes cellular senescence and inflammation.

Ramabadran et al. identify a DNA methylation-independent role for DNMT3A in stem cell activation, mediated through recruitment of SF3B1 and splicing regulation.

Mangione et al. report that sensory bristles co-opt neighbouring epidermal cells, which adopt a special morphology and contribute to touch sensing in Drosophila.

Gioia, Tavella et al. show that severe acute respiratory syndrome coronavirus 2 causes DNA damage through CHK1 degradation and impairs 53BP1 recruitment to DNA lesions. The induced DNA damage is associated with expression of pro-inflammatory cytokines and senescence markers.

Rubio-Navarro et al. identify a subset of pancreatic beta cells marked by high CD63 levels with enhanced glucose-stimulated insulin secretion. CD63-high beta cells are diminished in mouse models of and in humans with type 2 diabetes.

Weigert et al. show that an antagonistic relationship between DNA methyltransferase and Polycomb activity is globally responsible for the maintenance of intermediate methylation levels observed in trophoblast stem cells.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

Xu et al. provide a single-cell transcriptomic atlas of 4–6 week human embryos, thereby profiling early human organogenesis.

Berg et al. describe Metaboverse, a tool for automated discovery and visualization of metabolic data. Metaboverse enhances the user’s ability to extract meaningful patterns from multi-omics datasets to describe metabolic responses and signatures.