Articles in 2022

Extracellular vesicles (EVs) mediate cell–cell communication in physiology and pathology but many questions remain about the mechanisms governing their delivery to recipient cells. This Expert Recommendation article highlights areas of progress and challenges in establishing the importance of EV-mediated communication in vivo.

Topoisomerases have essential roles in transcription, DNA replication, chromatin remodelling and, as recently revealed, 3D genome organization. However, topoisomerases also generate DNA–protein crosslinks coupled with DNA breaks, which are increasingly recognized as a source of disease-causing genomic damage.

The regulatory sequences carried by transposable elements (TEs) often recruit the transcription machinery and affect host gene expression. Recent studies have revealed mechanisms by which TEs contribute to transcription regulation, including donation of enhancer and promoter sequences, modification of 3D chromatin architecture, and generation of novel regulatory non-coding RNAs and transcription factors.

The metabolism of somatic stem cells must be regulated to meet their specific needs, to enable long-term maintenance as well as their activation, proliferation and subsequent differentiation. Better understanding of metabolic regulation in stem cells will open new opportunities to manipulate stem cell function, with potential applications in tissue regeneration and cancer prevention.

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.

Ma and Xu discuss the status, best practices and future of using deep learning methods to analyse single-cell data.

Irene Miguel-Aliaga comments on the importance of considering biological sex as an experimental variable.

Reactive oxygen species (ROS) comprise a wide variety of oxidant molecules with vastly different properties and biological functions in physiology and in disease. Approaches to characterize oxidants in the in vivo context and identify their specific cellular targets will be required to understand and control the pathophysiological activities of ROS.

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.

Olivier Voinnet proposes that movement of gene-silencing small RNAs (sRNAs) in plants can be regulated by intracellular sRNA biogenesis and activity factors expressed in silencing-signal emitting, traversed and recipient cells.

E3 ubiquitin ligases ensure the precise spatiotemporal control of key molecules during important cellular processes. This Review discusses the crucial roles of E3 ligases during early mammalian development and their roles in human disease, and considers how new methods to manipulate the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.

Mammalian RNA polymerase II transcribes protein-coding genes and non-coding transcription units, including long non-coding RNAs (lncRNAs). Studies applying recently developed nascent transcriptomics technology have revealed differences in transcription initiation and termination between lncRNAs and protein-coding genes, bearing relevance to genomic stress and DNA damage.

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.

The majority of macromolecules are transported across the nuclear membrane by the Karyopherin-β (Kap) proteins, comprising importins, exportins and biportins. Unravelling mechanisms and regulation of Kap–cargo interactions is essential for understanding nuclear export and import of proteins and RNA and how this traffic impacts their physiological functions.

Lysine acetyltransferases and lysine deacetylases regulate gene expression and protein function by controlling acetylation and deacetylation of histones and diverse non-histone proteins. The activity of lysine acetyltransferases and lysine deacetylases is regulated by cellular metabolic states, offering the potential for therapeutic modulation through dietary and pharmacological interventions.