Articles in 2021

An emerging model of gene regulation posits that DNA, RNA and proteins form condensate nuclear compartments that facilitate cooperative interactions. This Review discusses how compartmentalization can lead to non-stoichiometric molecular interactions and behaviours in transcription, co-transcriptional and post-transcriptional RNA processing, and higher-order chromatin regulation.

Jonathon Ditlev shares his thoughts on building a research programme in a competitive field.

RNA interference mediated by a Dicer isoform protects mammalian stem cells against RNA viruses.

Meng Wang discusses the importance of early studies that led to the discovery of genes that regulate longevity.

Following their biogenesis, autophagosomes undergo maturation into degradative autolysosomes by fusing with late endosomes/lysosomes. This process — involving an array of molecular regulators of membrane dynamics — is essential for autophagic degradation, and its deregulation can lead to disease, including neurodegeneration, muscle diseases and cancer, and propagation of pathogens.

Izabela Sumara highlights the work by Beck and colleagues that identified a pathway for the biogenesis of nuclear pore complexes, which involves annulate lamellae and biomolecular condensates containing nucleoporins.

Insulin resistance is one of the earliest manifestations of several human diseases, including type 2 diabetes and cardiovascular disease. This Review discusses the causes of insulin resistance and recent insights into the underlying mechanisms, providing directions for the development of novel therapeutic strategies

Rippe and Papantonis suggest that intrinsically disordered regions in transcription-relevant factors underlie the formation of both ‘transcriptional condensates’ and ‘transcription factories’.

Stem cells are well known to be controlled transcriptionally, but recent studies indicate that pluripotency, cell fate and differentiation depend on the regulation of translation and ribosome biogenesis by mTOR signalling, ribosome levels, and mRNA and tRNA features. Elucidating these stem cell regulatory mechanisms may increase our understanding of tumorigenesis.

The pathogenicity of SARS-CoV-2 and respiratory syncytial virus (RSV) involves mechanisms of liquid–liquid phase separation, which can be explored as targets for new antiviral therapeutics.

Myopathies are genetically inherited diseases that affect the structure and/or function of skeletal muscles and often result in muscle degeneration (muscular dystrophy). This Review discusses our current understanding of the cellular and molecular mechanisms that underlie the most common of these pathologies, which provide key insights into muscle biology.

Apoptotic hair follicle stem cells contribute to tissue regeneration by producing WNT3, which promotes cell proliferation, enlarging the stem cell pool.

Eric Wang’s familial connection to disease raised tension between efforts devoted to fundamental versus translational research — until he realized both synergize.

In response to replication stress, TOPBP1 is recruited by Treacle to nucleoli, where the two proteins facilitate the stress response and help maintain the transcription of rRNA genes.

The orientation of cell divisions regulates tissue architecture and cell fate and depends on mitotic spindle positioning, which is controlled by intracellular and extracellular cues. Building on work in invertebrate systems, recent studies addressed how these mechanisms operate in vertebrates, and provided initial insights into their roles in vertebrate tissue development and homeostasis.

Expansion of short tandem repeats can impair RNA and protein function and cause diseases through four main mechanisms: transcription repression, RNA gelation and sequestration of RNA-binding proteins, protein gain of function, and repeat-associated non-AUG toxic translation. Synergy between these mechanisms exacerbates disease, but also offers promising therapeutic targets.

Torrino et al. show that the stiffness of the extracellular matrix regulates microtubule posttranslational modification via glutamylation, which impacts microtubule dynamics and cell invasiveness.

Migrasomes function as a mitochondrial quality control mechanism in migrating cells, and affect neutrophil viability.

Bacteriophage anti-CRISPR proteins evolved to counter CRISPR–Cas-mediated immunity in prokaryotes. Recent structural studies have provided novel insights into the mechanisms and functions of anti-CRISPRs, and have increased the breadth of their use for biotechnology applications in eukaryotes.