Volume 24 Issue 4, April 2022

Biomolecular condensation has emerged as a fundamental mechanism for cellular organization, but less is known about the regulation of condensate subcellular location and size. A new study reports that membrane tethering of protein and RNA directly influences the assembly, size and material properties of ribonucleic condensates.

Necrosomes formed by RIPK1–RIPK3 mediate necroptosis. Super-resolution microscopy identifies the architectural features of necrosomes and provides mechanistic insights into the signalling from RIPK1 to RIPK3 when RIPK1 is activated to mediate necroptosis, and from RIPK3 to RIPK1 when RIPK3 is inhibited to mediate apoptosis.

Overload of proteasomal clearance triggers formation of a large protein inclusion called the aggresome, which shares similarities with protein aggregates seen in neurodegenerative diseases such as Huntington’s. A new study uncovers how centrosome and centriolar satellite components facilitate stepwise assembly of aggresomes.

Organic acidurias are inherited disorders that can severely affect mitochondria. A study in Caenorhabditis elegans suggests that binding of a toxic metabolite to a factor crucial for mitochondrial structure may contribute to disease mechanisms.

Epithelial to mesenchymal transitions (EMTs) drive cancer metastases. A series of single cell analyses now reveal this change in state is not binary and that two epigenetic complexes govern the convertibility of epithelial cells to mesenchymal states that are differentially conducive to metastasis.

Shi et al. discuss recent approaches for the discovery of small noncoding RNAs (sncRNAs), limitations associated with sncRNA expression analyses, and emerging methods for direct and simultaneous detection of multiple RNA modifications.

Merino et al. report that the cell-death factor Flower can control responses to morphogen gradients and thus has a role in gradient scaling.

Fort et al. implicate apoptosis and an epithelial-to-mesenchymal transition in the cardiomyocyte conversion of human stem cells. Nucleotides released from dying cells act through P2Y2 receptors on surviving cells to license WNT-dependent mesoderm specification.

Tang et al. report that sequential epigenetic remodelling of mesendoderm enhancers is required for the segregation of human primordial germ cell and mesendodermal cell fates.

Snead et al. report that membrane tethering facilitates assembly of ribonucleoprotein condensates while also restricting condensate size by reducing the diffusion of protein and RNA.

Chen et al. examine the cellular necrosome using STORM and uncover the rod-shaped structure formed by mosaics of RIP1 and RIP3 oligomers.

Prosser et al. report that centriolar satellite and centrosomal proteins seed aggresomes, perinuclear inclusions of misfolded proteins, and may play a role in aggresome formation during senescence and huntingtin aggregation.

Zhou and colleagues identify SNX4–SNX5–SNX17 as a multiunit complex that mediates the recycling of autophagosomal components from autolysosomes.

Fu, et al. report that PARP1-dependent poly(ADP-ribsoyl)ation of the P-TEFb subunit CycT1 suppresses its phase separation, which prevents its interaction partner CDK9 from hyperphosphorylating RNA polymerase II and thereby blocks transcription.

Zhou, Duan, Wang et al. show that d-2-hydroxyglutarate affects mitochondrial health by inhibiting the 3-hydroxypropionate (3-HP) dehydrogenase HPHD-1, leading to a build-up of 3-HP and interference with IMMT-1 (also knowns as MIC60) function in mitochondria structure.

Crist et al. show that tumour cells disseminate and accumulate in skeletal muscle but fail to proliferate and grow due to oxidative stress, thereby explaining why skeletal muscle is resistant to metastatic colonization and outgrowth.

Through genome-wide and focused CRISPR screens, Zhang et al. discover that loss of PRC2 or KMT2D-COMPASS enables distinct EMT trajectories, which exert differential effects on the metastatic capability of carcinoma cells.

Abe et al. profile, characterize and compare non-haematopoietic cells in normal human lymph nodes versus nodal lymphomas from patients, providing insights into stromal modelling in health and disease.

Lummertz da Rocha et al. present CellComm, an algorithm that analyses cell–cell communication to predict signalling and regulatory networks, and identify regulators of haematopoietic development in the aorta–gonad–mesonephros region.

Through structure-guided protein engineering, Guo et al. developed a Lachnospiraceae bacterium Cas12a variant with enhanced editing efficiency and applied the enzyme-dead version of this variant for multiplex gene activation in the mouse retina.