Reviews & Analysis

Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, autophagy supports tissue and organismal fitness and promotes longevity. Thus, autophagy induction could be considered a strategy to extend lifespan.

Core promoters of RNA polymerase II enable highly regulated transcription initiation by integrating cues from distal enhancers. The emerging diversity of core promoters defines distinct transcription programmes and can explain the nature and outcome of transcription initiation at gene start sites and at enhancers.

Metabolism feeds into gene regulation, allowing adaptation of gene expression to satisfy cellular needs, including in pathological scenarios such as cancer. Metabolism modulates gene expression through metabolites, which serve as cofactors for DNA and histone modifiers, and through metabolic enzymes, which locally regulate chromatin and transcription in the nucleus.

Decline in stem cell function causes loss of tissue homeostasis and increased incidence of age-related diseases. During ageing, adult stem cells accumulate damage and the niche in which they reside malfunctions. These defects are associated with changes in the epigenome that contribute to organ dysfunction and disease.

Taking advantage of genetic engineering, synthetic biology allows control and design of new cell functions. Recent advances in the development of genetic tools and the assembly of progressively more sophisticated gene circuits have made ‘designer cells’ a reality, with applications ranging from industry and biotechnology to medicine.

The tumour suppressor PTEN regulates various cellular processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. Recent studies into the regulation of PTEN levels and activity provide new insights into its anti-oncogenic functions and offer novel opportunities for cancer treatment.

DNA methylation in plants mediates gene expression, transposon silencing, chromosome interactions and genome stability. It is therefore not surprising that the regulation of DNA methylation is important for plant development and for plant responses to biotic and abiotic stresses.

Ribosomes encounter obstacles during translation elongation that cause their stalling and can have a profound impact on protein yield. Ribosome stalling depends on the genetic code, amino acid availability, regulatory elements and mRNA context and can be resolved by resumption of translation or by ribosome rescue and recycling.

Transcription elongation by RNA polymerase II (Pol II) involves pausing of Pol II at promoter-proximal regions. Pol II release into gene bodies (productive elongation) is controlled by many transcription-specific factors, enhancers and factors that are canonically associated with genome maintenance.

The maternal-to-zygotic transition (MZT) is defined as the transition from maternal gene expression in the oocyte to zygotic genome activation and embryonic-driven development. Recent studies have improved our understanding of the dynamics of the MZT, which is characterized by global DNA demethylation, chromatin remodelling, genome reorganization and substantial transcriptional changes.

Microtubules are highly dynamic tubulin polymers, and their dynamics are associated with a conformational cycle of individual tubulin subunits in the lattice. Recent evidence suggests that fine-tuning microtubule dynamics is enabled by the allosteric coupling of tubulin subunits, which propagates conformational changes through the lattice.

Single-cell technologies are transforming our understanding of pre-implantation and early post-implantation development and of in vitro pluripotency. Specifically, single-cell transcriptomics and imaging and the accompanying bioinformatics methods have enabled precision interrogation of cell fate choices and cell lineage diversification, which occur at the level of the individual cell.

Cytoplasmic dynein is a minus-end-directed microtubule-based motor that transports a wide range of cargoes, including organelles, RNAs, protein complexes and viruses. How a single motor can interact with and traffic such different cargoes has been unclear. Recent studies indicate how adaptor proteins, which can both activate dynein and link it to cargo, play an important role in this process.

Transforming growth factor-β (TGFβ) family cytokines are important regulators of cell fate with pleiotropic roles in development, tissue homeostasis, regeneration and tumorigenesis. Recent studies revealed that this context dependency relies on the convergence between TGFβ signals and other contextual inputs, whereby transcription factors downstream of these pathways collaboratively act to regulate gene expression.

The selective degradation of cellular components via chaperone-mediated autophagy (CMA) functions to regulate a wide range of cellular processes, from metabolism to DNA repair and cellular reprogramming. Recent in vivo studies have enabled to dissect key roles of CMA in ageing and ageing-associated disorders such as cancer and neurodegeneration.

Autophagy is a process of cellular self-consumption that promotes cell survival in response to stress. Various human pathologies, including cancer, neurodegeneration and inflammation, have been associated with aberrant autophagy, and recent studies of the mechanisms and regulation of autophagy in higher eukaryotes have suggested new therapeutic possibilities.

Clathrin-mediated endocytosis is the main mechanism for internalization of cell-surface molecules and surface-bound cargoes. Although the machineries that drive the formation of endocytic vesicle are intricate, an understanding of endocytosis is being unravelled at the molecular level.

Membrane lipids exhibit a remarkable diversity — they vary in structure and chemical properties, and their distribution between different membranes and their subcompartments is highly heterogeneous. Recent progress in studies of membrane lipids has broadened our understanding of how this diversity affects membrane properties and membrane-associated processes.

Most eukaryotic cells contain a single centrosome with a pair of centrioles, which duplicate before mitosis. Defects in duplication lead to aberrant numbers of centrioles and centrosomes. Recent insights into mechanisms of centriole biogenesis and centriole number control are helping us to better understand the links between aberrant centrosome number and human disease.

Recent studies that combine cell biology, structural and proteomic approaches have unravelled how ubiquitin is conjugated to damaged mitochondria through the PINK1–parkin pathway to promote mitophagy. The findings have revealed links between PINK1–parkin, antigen presentation and neuronal survival and have implications for the understanding of neurological disorders.