The non-coding RNA 7S inhibits transcription initiation in mitochondria by preventing the RNA polymerase from interacting with promoter DNA and transcription factors.

RNA silencing is a well-established antiviral immunity system in plants, in which small RNAs guide Argonaute proteins to targets in viral RNA or DNA, resulting in virus repression. Virus-encoded suppressors of silencing counteract this defence system. In this Review, we discuss recent findings about antiviral RNA silencing, including the movement of RNA through plasmodesmata and the differentiation

Rensvold et al. provide a resource to characterize the function of mitochondrial proteins and to facilitate the discovery of disease-relevant mutations.

James Olzmann discusses the groundbreaking work of Ron Kopito and colleagues, which demonstrated that a CFTR mutant is ubiquitinated and degraded by the cytosolic 26S proteasome. This discovery contributed to our understanding of ERAD and had important implications for the development of therapeutic agents for cystic fibrosis.

XIST loss causes partial gene reactivation at the inactive X chromosome, resulting in Mediator-dependent expansion of adult mammary stem cells and tumorigenesis.

The active transport of organelles and other cargos along the axon is required to maintain neuronal health and function, but we are just beginning to understand the complex regulatory mechanisms involved. The molecular motors, cytoplasmic dynein and kinesins, transport cargos along microtubules; this transport is tightly regulated by adaptors and effectors. Here we review our current understanding

Phosphoinositides are signalling lipids derived from phosphatidylinositol, a ubiquitous phospholipid in the cytoplasmic leaflet of eukaryotic membranes. Initially discovered for their roles in cell signalling, phosphoinositides are now widely recognized as key integrators of membrane dynamics that broadly impact on all aspects of cell physiology and on disease. The past decade has witnessed a vast

Cail et al. introduce a platform to study the role of plasma membrane curvature during clathrin-mediated endocytosis.

Transcriptional regulation of catabolic pathways is a central mechanism by which cells respond to physiological cues to generate the energy required for anabolic pathways, transport of molecules and mechanical work. Nuclear receptors are members of a superfamily of transcription factors that transduce hormonal, nutrient, metabolite and redox signals into specific metabolic gene programmes, and thus

Heterochromatin is characterized by dimethylated or trimethylated histone H3 Lys9 (H3K9me2 or H3K9me3, respectively) and is found at transposable elements, satellite repeats and genes, where it ensures their transcriptional silencing. The histone methyltransferases (HMTs) that methylate H3K9 — in mammals Suppressor of variegation 3–9 homologue 1 (SUV39H1), SUV39H2, SET domain bifurcated 1 (SETDB1)

Plant hormones are signalling compounds that regulate crucial aspects of growth, development and environmental stress responses. Abiotic stresses, such as drought, salinity, heat, cold and flooding, have profound effects on plant growth and survival. Adaptation and tolerance to such stresses require sophisticated sensing, signalling and stress response mechanisms. In this Review, we discuss recent

As the home of cellular genetic information, the nucleus has a critical role in determining cell fate and function in response to various signals and stimuli. In addition to biochemical inputs, the nucleus is constantly exposed to intrinsic and extrinsic mechanical forces that trigger dynamic changes in nuclear structure and morphology. Emerging data suggest that the physical deformation of the nucleus

Kate Meyer reminds us of a study of mRNA N6-methyladenosine that predated the epitranscriptomics era by decades.

H3K9me3 promotes imprinting in mouse embryos, including in a newly discovered type of imprinting control-like regions.

The eukaryotic transcription apparatus synthesizes a staggering diversity of RNA molecules. The labour of nuclear gene transcription is, therefore, divided among multiple DNA-dependent RNA polymerases. RNA polymerase I (Pol I) transcribes ribosomal RNA, Pol II synthesizes messenger RNAs and various non-coding RNAs (including long non-coding RNAs, microRNAs and small nuclear RNAs) and Pol III produces

A Comment on the impact of improved protein structure prediction by Kathryn Tunyasuvunakool from DeepMind — the company behind AlphaFold. The 2020 Critical Assessment of protein Structure Prediction (CASP) marked a significant advance. The machine learning method AlphaFold predicted the structure of most target proteins to an accuracy assessors called “competitive with experiment”. Here, I discuss

RNA–DNA hybrids are generated during transcription, DNA replication and DNA repair and are crucial intermediates in these processes. When RNA–DNA hybrids are stably formed in double-stranded DNA, they displace one of the DNA strands and give rise to a three-stranded structure called an R-loop. R-loops are widespread in the genome and are enriched at active genes. R-loops have important roles in regulating

Viegas and Figueiredo tell us how, among several molecular and biochemical discoveries, RNA trans-splicing was discovered in trypanosomes.

Epithelial cells are the most common cell type in all animals, forming the sheets and tubes that compose most organs and tissues. Apical–basal polarity is essential for epithelial cell form and function, as it determines the localization of the adhesion molecules that hold the cells together laterally and the occluding junctions that act as barriers to paracellular diffusion. Polarity must also target

Mori et al. identify ATP and reactive oxygen species as key upstream cues for cell extrusion.

The discovery of diverse chemical modifications of mRNA has spurred efforts to identify, map and characterize them. Yet aside from N6-methyladenosine (m6A), progress in epitranscriptomics has been stymied by discrepant data. Here we discuss the main obstacles in studying novel mRNA modifications and offer insights into how to surmount them. Progress in the characterization of new mRNA modifications

Heterochromatin DNA is heavily methylated yet also inaccessible. Olivier Mathieu describes the work that revealed how DNA methyltransferases access heterochromatin.

The transcription factor c-Maf is required for the specification of liver sinusoids and for the maintenance of a specialized sinusoidal network necessary for sustaining hepatocyte function.

Ma et al. show the role of CCT2, a chaperonin TRiC subunit, in aggrephagy, specifically in the removal of mature, solid-like protein aggregates.

Microtubules are polarized cytoskeletal filaments that serve as tracks for intracellular transport and form a scaffold that positions organelles and other cellular components and modulates cell shape and mechanics. In animal cells, the geometry, density and directionality of microtubule networks are major determinants of cellular architecture, polarity and proliferation. In dividing cells, microtubules

Mechanical signalling affects multiple biological processes during development and in adult organisms, including cell fate transitions, cell migration, morphogenesis and immune responses. Here, we review recent insights into the mechanisms and functions of two main routes of mechanical signalling: outside-in mechanical signalling, such as mechanosensing of substrate properties or shear stresses; and

Returning to the lab after a career break can be a daunting prospect even if you have only been away for a year. My time away lasted 12 years, which meant I was returning to a whole new era in science. Jane Skok recounts her journey back to academia after a 12-year-long career break.

The solid phase of oskar mRNA granules is required for proper Oskar protein synthesis and fruit fly development.

Arnold et al. document an alternative tricarboxylic acid cycle that takes place between the mitochondria and the cytosol and that can be adopted in specific cell states.

Transposons and their host genomes are entangled in an evolutionary arms race, recounts Tuğçe Aktaş.

Pioneer factors are transcription factors with the unique ability to initiate opening of closed chromatin. The stability of cell identity relies on robust mechanisms that maintain the epigenome and chromatin accessibility to transcription factors. Pioneer factors counter these mechanisms to implement new cell fates through binding of DNA target sites in closed chromatin and introduction of active-chromatin

The RNA-binding proteins RBGD2 and RBGD4 improve resistance to heat stress in plants by phase separating into heat-induced stress granules.

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. They have important roles in numerous physiological and pathological processes, and show considerable promise as novel biomarkers of disease, as therapeutic agents and as drug delivery vehicles. Intriguingly, however, understanding of the cellular and molecular mechanisms that govern the

Human topoisomerases comprise a family of six enzymes: two type IB (TOP1 and mitochondrial TOP1 (TOP1MT), two type IIA (TOP2A and TOP2B) and two type IA (TOP3A and TOP3B) topoisomerases. In this Review, we discuss their biochemistry and their roles in transcription, DNA replication and chromatin remodelling, and highlight the recent progress made in understanding TOP3A and TOP3B. Because of recent

Transposable elements (TEs) comprise about half of the mammalian genome. TEs often contain sequences capable of recruiting the host transcription machinery, which they use to express their own products and promote transposition. However, the regulatory sequences carried by TEs may affect host transcription long after the TEs have lost the ability to transpose. Recent advances in genome analysis and

Metabolism has been studied mainly in cultured cells or at the level of whole tissues or whole organisms in vivo. Consequently, our understanding of metabolic heterogeneity among cells within tissues is limited, particularly when it comes to rare cells with biologically distinct properties, such as stem cells. Stem cell function, tissue regeneration and cancer suppression are all metabolically regulated

Ting and Lee describe how the trypanosome base J ‘inspired’ the discovery of the mechanism of active DNA demethylation.

Highly transcribed long genes ‘stiffen’ and form loops extending from the harbouring chromosomes.

Deep learning has tremendous potential in single-cell data analyses, but numerous challenges and possible new developments remain to be explored. In this commentary, we consider the progress, limitations, best practices and outlook of adapting deep learning methods for analysing single-cell data. Ma and Xu discuss the status, best practices and future of using deep learning methods to analyse single-cell

You spent years investigating your beloved protein. You generated mouse models, found a phenotype and fixed it with a drug. You even used human cells to reveal a conserved mechanism. But a prestigious journal has rejected your manuscript because you did not include females. Here is why you should not be mad at them. Irene Miguel-Aliaga comments on the importance of considering biological sex as an

‘Reactive oxygen species’ (ROS) is a generic term that defines a wide variety of oxidant molecules with vastly different properties and biological functions that range from signalling to causing cell damage. Consequently, the description of oxidants needs to be chemically precise to translate research on their biological effects into therapeutic benefit in redox medicine. This Expert Recommendation

Jijumon et al. introduce a straightforward, cell-free assay to unravel the functions of microtubule-associated proteins.

Keren Lasker discusses early work of Lucy Shapiro, which provided first evidence that bacterial cells spatially regulate their cellular processes, akin to their eukaryotic counterparts.

A long non-coding RNA is found to enable the assembly of a glycolytic metabolon that contributes to cell adaptation to metabolic stress and cell survival.

Pseudouridylation of pre-mRNA can broadly modulate alternative splicing in human cells.

Regulation of intercellular small RNA (sRNA)-mediated gene silencing in plants is commonly ascribed to hypothetical mechanisms involving movement channels. In this commentary, I present a complementary, perhaps counter-intuitive view, in which sRNA movement is also crucially regulated by the cell-autonomous silencing machinery found in silencing-emitting, traversed and recipient cells. Olivier Voinnet

Mammalian development demands precision. Millions of molecules must be properly located in temporal order, and their function regulated, to orchestrate important steps in cell cycle progression, apoptosis, migration and differentiation, to shape developing embryos. Ubiquitin and its associated enzymes act as cellular guardians to ensure precise spatio-temporal control of key molecules during each of

Mammalian genomes express two principal gene categories through RNA polymerase II-mediated transcription: protein-coding transcription units and non-coding RNA transcription units. Non-coding RNAs are further divided into relatively abundant structural RNAs, such as small nuclear RNAs, and into a myriad of long non-coding RNAs (lncRNAs) of often low abundance and low stability. Although at least some

Valeria Levi recounts how a clever way to visualize the function of H+-ATP synthase pioneered single-molecule technologies.

‘Alpha helix’ was not Linus Pauling’s first choice of a name for the protein structural motif. Egli and Zhang recount what the original name was, why it was changed and what is between the alpha helix and the DNA double helix.

Efficient and regulated nucleocytoplasmic trafficking of macromolecules to the correct subcellular compartment is critical for proper functions of the eukaryotic cell. The majority of the macromolecular traffic across the nuclear pores is mediated by the Karyopherin-β (or Kap) family of nuclear transport receptors. Work over more than two decades has shed considerable light on how the different Kap

Lysine acetylation is a widespread and versatile protein post-translational modification. Lysine acetyltransferases and lysine deacetylases catalyse the addition or removal, respectively, of acetyl groups at both histone and non-histone targets. In this Review, we discuss several features of acetylation and deacetylation, including their diversity of targets, rapid turnover, exquisite sensitivity to

Rana et al. show that in the gut epithelium, gasdermin B has an inherent, non-pyroptotic function, supporting the maintenance of the epithelial barrier when challenged with inflammatory damage.

Mike Henne discusses the pioneering work of Jean Vance, which revealed that mitochonodria-associated membranes (MAMs) are sites for inter-organelle phospholipid exchange and step-wise synthesis reactions.

Prior to introduction of the first DNA–protein structure, Ned Seeman et al. correctly conceived how proteins recognize specific sequences in double-helix nucleic acids.