News & Views

The onset of differentiation has been assumed to follow withdrawal from the cell cycle. A new study shows that keratinocytes initiate differentiation before exiting the cell cycle, allowing the skin to respond rapidly to damage.

Several new technologies have used synthetic RNAs that leverage the cell’s RNA splicing machinery to drive the expression of gene products. A new study now reports a technique to dynamically and non-invasively monitor gene expression by embedding reporters within introns contained in the parent gene.

FG-nucleoporins of the nuclear pore complexes form a permeability barrier between the nucleus and the cytosol. FG-nucleoporins contain disordered regions and are prone to aggregation. Two studies identify the chaperone DNAJB6 as a key factor that prevents aggregation of FG-nucleoporins and assists in the biogenesis of nuclear pore complexes.

PTEN, a tumour suppressor, also regulates T cell activation. A new study reports that PTEN acts as a cell-intrinsic rheostat linking TCR- and IL-23-mediated signalling to regulate development of type-17 innate-like T cells in the thymus. This work may have important implications for treating autoimmune and inflammatory diseases.

In tumours, cancer cells can overcome energy stress via differential regulation of non-canonical ‘moonlighting’ functions of metabolic enzymes. A study now shows that the metabolic phosphatase fructose-1,6-bisphosphatase 1 (FBP1) can act as a nuclear protein phosphatase and reveals how this process is inhibited in cancer cells.

Specialized activities of ribosomal components that regulate the expression of specific genes is an emerging field of research. A new study identifies alternative splicing of a ribosomal protein between the peripheral and core regions of glioblastoma tumours to produce isoforms with distinct functions.

Cellular senescence induced by DNA replication and telomere attrition contributes to organ dysfunction, inflammation and impaired immunity. A study reveals that antigen-presenting cells provide telomeric DNA to CD4⁺ T cells in synaptic contact, which enables the suspension of senescence, T cell expansion and long-lived immunity.

The Rag GTPases form the link between extracellular nutrients and the activation of mTORC1. RagA/B and RagC/D have been considered functionally redundant, but two studies now show that each isoform and gene have specific features, making their control of mTORC1 activity more nuanced and complex than previously appreciated.

Aggregation of the RNA-binding protein TDP-43 is commonly observed in neurodegenerative disorders. A new study reveals that this process may be blocked by HSPB1, a small heat shock protein that can also regulate TDP-43 phase separation. This may be relevant to neurodegeneration, as loss of HSPB1 correlates with TDP-43 pathology.

The mechanisms that underlie cell identity remain poorly understood. A study now dissects the transcriptional trajectories of single cells undergoing malignant transformation or reprogramming to pluripotency and reveals regulators of cell plasticity in these biological processes.

NADPH levels serve as a biomarker of sensitivity to ferroptosis, but the regulators that detect cellular NADPH levels and modulate downstream ferroptosis responses are unknown. A study now identifies MARCHF6 in the ubiquitin system as an NADPH sensor that suppresses ferroptosis.

Aberrant subcellular localization of proteins contributes to the pathogenesis of cancer. A study now reports that the mis-localization of METTL3, a nuclear N⁶-adenosine methyltransferase, to the cytoplasm promotes gastric cancer by enhancing mRNA translation of a subset of oncogenes, independently of the N⁶-methyladenosine (m⁶A) modification.

EGFR is an oncogene that is frequently amplified in glioblastoma. A new study suggests a tumour-suppressive role of EGFR in EGFR-amplified glioblastoma regulated by ligand abundance. Increased EGFR ligand in EGFR-amplified glioblastoma suppresses invasion by upregulating BIN3 and inhibiting activation of Rho GTPases.

Primary cilia transduce cues, including Hedgehog (Hh) signals, and possess doublet microtubules that interact with kinesin motors. The kinesin KIF7 is important for Hh signalling and binds to GLI transcription factors. Haque et al. reveal that, surprisingly, GLI proteins bind a DNA-like part of KIF7 to promote their accumulation at the ciliary tip.

Intrinsically disordered regions are a ubiquitous class of protein domains that lack a fixed 3D structure. Here, an evolutionarily conserved family of disordered CO₂ sensors has been discovered, expanding the growing repertoire of disordered regions that respond to changes in the cellular environment.

In Caenorhabditis elegans, RNAi-initiated gene silencing can persist for multiple generations. A study shows that this heritable silencing requires parallel contributions of both a nuclear transcriptional silencing pathway and perinuclear condensate-localized poly(UG)-tailed transcripts to produce abundant germline siRNAs in adult progeny.

Multiple methods for deriving human cortical organoids have been established in the past decade. A study now systematically compares patterning strategies and shows that combined WNT and dual SMAD inhibition is superior to dual SMAD inhibition alone in inducing robust cortical identity in 3D human pluripotent stem-cell aggregates.

Human naive pluripotent stem cells are generally believed to possess an unrestricted capacity to differentiate into both embryonic and extraembryonic lineages. However, two new studies now uncover a role for the Polycomb repressive complex 2 (PRC2) as a lineage gatekeeper that shields the potency of these cells.

The lysosome is an essential organelle that degrades extra- and intra-cellular components and acts as a signaling hub. A study in Caenorhabditis elegans now shows that the lysosome mediates inter-tissue communication from periphery to neurons to regulate lifespan via fatty acid breakdown and secretion.

The nuclear pore complex (NPC) regulates transport of macromolecules into and out of the nucleus. A study now shows that mechanical force applied on the nucleus affects the transport rates across the NPC diffusion barrier, modulating the nuclear localization of certain cargos.