Review Articles

RNA-binding proteins (RBPs) are essential for gene regulation. Recent data reveal that small biomolecules (SBMs) such as sugars, nucleotides, metabolites and drugs bind to RBPs and regulate their function. This Review discusses the landscape of SBM-binding RBPs, the molecular basis of their interactions and their relevance to human diseases.

Hsp70 chaperones facilitate protein folding, complex assembly and translocation through membranes. This Review discusses recent insights into how Hsp70 and its co-chaperones — J-domain proteins and nucleotide exchange factors — exert such functions, achieve substrate specificity and determine protein fate (folding or degradation).

Co-transcriptional mRNA maturation is a complex, multistep process. This Review focuses on how the development of long-read sequencing methods enabled investigating the timing, coordination and outcomes of alternative uses of transcription start sites, splice sites and polyadenylation sites and their disease implications.

Protein tyrosine phosphatases (PTPs) regulate cell signalling and contribute to a wide range of human diseases. This Review discusses mechanistic insights into PTP function and regulation, their physiological roles and the development of PTP-targeted therapeutics.

The development of a functional heart depends on the specification of multiple cell types, including pacemaker cells, and complex tissue re-organization. This Review discusses recent insights into these processes from in vivo studies and cardiac organoid models.

Human germ cells are specified during early development and eventually differentiate into sperm and oocytes. Recent studies have revealed key signalling pathways and epigenetic mechanisms of their development, enabling in vitro reconstitution and potential treatments for germ cell-related diseases.

The use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

Recent near-atomic structures of the nuclear pore complex provide insights into its assembly and function — how it acts as a selective permeability barrier, regulates nucleocytoplasmic transport such as mRNA export, and integrates mechanical forces experienced by the cell and nucleus.

Lys l-lactylation of histones is a newly identified short-chain acylation that regulates transcription and other cellular processes, with diverse pathophysiological outcomes, notably in cancer. This Review discusses the unique biochemical features of Lys l-lactylation and its dynamic regulation by various metabolism-related mechanisms.

Lysosomes degrade cellular components, and their membrane is an important signalling hub. Recent insights into the mechanisms that maintain lysosomal membrane homeostasis — including the interplay between membrane damage, repair, lysophagy and lysosome biogenesis — highlight their importance in physiology, in disease and during ageing.

This Review discusses new mechanistic insights into plant microRNA maturation, intercellular and tissue mobility and the intriguing interplay between microRNAs and the translation process.

Degrons allow E3 ubiquitin ligases to identify their substrates, and thus have a central role in protein degradation by the ubiquitin–proteasome system. This Review discusses the latest insights into the mechanisms underlying degron function, the relevance of degrons in disease and how degrons can be harnessed for therapeutic protein degradation.

Mitochondrial proteins encoded in the nucleus are imported into mitochondria by specialized transport machineries located in the outer and inner mitochondrial membranes. This Review explores these diverse import pathways and highlights recent insights into the structural properties of the transport machinery.

Mammalian caspases are a group of cysteine proteases historically categorized into an ‘inflammatory’ subgroup and an ‘apoptotic’ subgroup, although accumulating evidence indicates that this distinction is not as clearcut as initially thought. Here, we discuss the functions of inflammatory caspases and apoptotic caspases, while proposing that all caspases ultimately regulate inflammation, either directly or by controlling cell death.

Transposable elements (TEs) comprise nearly half of the human genome. This Review discusses transcriptional and post-transcriptional mechanisms that repress TE activity, how TEs escape this suppression and regulate endogenous genes in development and disease, and emerging therapeutic strategies that exploit TE derepression.

Collective cell migration has major roles in animal development, tissue repair and cancer metastasis. This Review explores how migrating collectives are organized in development versus cancer, focusing on cell adhesion, signalling and guidance cues.

The electron transfer chain in chloroplast thylakoid membranes uses solar energy to produce NADPH and ATP, which power carbon fixation into biomass. This Review discusses the structure and function of the core photosynthesis complexes and provides recent insights into their regulation and assembly.

Pseudouridine is a long-discovered RNA modification that has lately attracted much renewed interest. This Review discusses the emerging functions of pseudouridine in gene regulation and mitochondrial function, and its therapeutic potential following the successful use of pseudouridylation in SARS-CoV-2 mRNA vaccines.

N-glycosylation of secretory pathway proteins in the ER is crucial for their maturation and quality control. Recent insights into the enzymes and chaperones that facilitate N-glycosylation have expanded our understanding of the glycoproteostasis network in metazoans.

The phytohormone auxin coordinates plant growth by forming local maxima and gradients through cell-to-cell transport and metabolic control. Recent research has identified novel signalling mechanisms involving extracellular auxin perception and auxin-mediated cyclic AMP production.