Wilfling et al. report a previously undescribed selective autophagy pathway that removes aberrant intermediates of clathrin-mediated endocytosis.

The journey of RNA polymerase II (Pol II) as it transcribes a gene is anything but a smooth ride. Transcript elongation is discontinuous and can be perturbed by intrinsic regulatory barriers, such as promoter-proximal pausing, nucleosomes, RNA secondary structures and the underlying DNA sequence. More substantial blocking of Pol II translocation can be caused by other physiological circumstances and

Mechanical forces shape cells and tissues during development and adult homeostasis. In addition, they also signal to cells via mechanotransduction pathways to control cell proliferation, differentiation and death. These processes require metabolism of nutrients for both energy generation and biosynthesis of macromolecules. However, how cellular mechanics and metabolism are connected is still poorly

Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties

This poster highlights the derivation and differentiation of human pluripotent stem cells and outlines key applications of these cells, such as cell-based therapies, disease modelling, drug discovery and the study of human development.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Giancarlo Abis recounts his inspiration for becoming a structural biologist — the publication of the HIV-1 RT structure, which enabled a therapeutic breakthrough.

RNA editing by ADAR1 destabilizes epigenetic-treatment-induced retrotransposon stem–loops and thus dampens the immune response to the treatment, suggesting that ADAR1 could be a therapeutic target in combination with epigenetic therapy.

Mitochondria contain about 1,000–1,500 proteins that fulfil multiple functions. Mitochondrial proteins originate from two genomes: mitochondrial and nuclear. Hence, proper mitochondrial function requires synchronization of gene expression in the nucleus and in mitochondria and necessitates efficient import of mitochondrial proteins into the organelle from the cytosol. Furthermore, the mitochondrial

Cell–cell interfaces are found throughout multicellular organisms, from transient interactions between motile immune cells to long-lived cell–cell contacts in epithelia. Studies of immune cell interactions, epithelial cell barriers, neuronal contacts and sites of cell–cell fusion have identified a core set of features shared by cell–cell interfaces that critically control their function. Data from

Glycosylation is the most abundant and diverse form of post-translational modification of proteins that is common to all eukaryotic cells. Enzymatic glycosylation of proteins involves a complex metabolic network and different types of glycosylation pathways that orchestrate enormous amplification of the proteome in producing diversity of proteoforms and its biological functions. The tremendous structural

Non-homologous DNA end joining (NHEJ) is the predominant repair mechanism of any type of DNA double-strand break (DSB) during most of the cell cycle and is essential for the development of antigen receptors. Defects in NHEJ result in sensitivity to ionizing radiation and loss of lymphocytes. The most critical step of NHEJ is synapsis, or the juxtaposition of the two DNA ends of a DSB, because all subsequent

Sheng-Cai Lin discusses discoveries implicating glycolytic enzyme, aldolase, in glucose sensing.

The discovery of the CRISPR–Cas9 system by Emmanuelle Charpentier and Jennifer Doudna awarded a 2020 Nobel Prize in Chemistry.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A signalling pathway comprising TMO5–LHW and cytokinin controls plant adaptation to low-phosphate levels in the soil by increasing root hair density.

Wozniak and colleagues reveal that cleavage of the lysosomal protein RILP following activation of the inflammasome enhances exosome release and regulates the trafficking of miRNAs into exosomes by FMR1.

The switch from glycolytic metabolism to OXPHOS functions as a driver of cell immortalization during tumorigenesis in the fly brain.

The prokaryote-derived CRISPR–Cas genome editing technology has altered plant molecular biology beyond all expectations. Characterized by robustness and high target specificity and programmability, CRISPR–Cas allows precise genetic manipulation of crop species, which provides the opportunity to create germplasms with beneficial traits and to develop novel, more sustainable agricultural systems. Furthermore

In the 20 years since human embryonic stem cells, and subsequently induced pluripotent stem cells, were first described, it has become apparent that during long-term culture these cells (collectively referred to as ‘pluripotent stem cells’ (PSCs)) can acquire genetic changes, which commonly include gains or losses of particular chromosomal regions, or mutations in certain cancer-associated genes, especially

Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells — combined with redundant sources of niche signals — enables

We reflect on the position of Nature Reviews Molecular Cell Biology, 20 years from its launch.

Storytelling provides a platform to learn, publish and share your science. Framing information into a compelling story can be a useful tool to disseminate your data and share your passion for science, to make a greater impact with your research and to advance your career. Rafael Luna uses his own experiences to illustrate the power of storytelling as a tool to share your science and advance your career

Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment — including inflammatory, endothelial and Schwann cells — persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through

The role of chromosome clustering as a driver of nucleo-cytoplasmic compartmentalization after mitosis.

The removal of functionally dispensable, infected or potentially neoplastic cells is driven by programmed cell death (PCD) pathways, highlighting their important roles in homeostasis, host defence against pathogens, cancer and a range of other pathologies. Several types of PCD pathways have been described, including apoptosis, necroptosis and pyroptosis; they employ distinct molecular and cellular

The nucleolus is the most prominent nuclear body and serves a fundamentally important biological role as a site of ribonucleoprotein particle assembly, primarily dedicated to ribosome biogenesis. Despite being one of the first intracellular structures visualized historically, the biophysical rules governing its assembly and function are only starting to become clear. Recent studies have provided increasing

A 2017 paper showed that phase separation and formation of elastin in the extracellular matrix does not require protein secondary structures, but cross-linked disordered chains.

Gavin Kelsey discusses the first reports of genomic imprinting in mammals and how they raised the profile of epigenetics in the study of mammalian development.

Sally Lowell discusses the concept of ‘community effect’ when cells commit to a certain differentiation path, which was proposed by John Gurdon in 1988 and recently suggested to enable cancer cells to gain control.

Twenty years ago it was reported that epithelial–mesenchymal transition (EMT), a key developmental process, occurs in cancer; many studies have since, and still are, studying EMT heterogeneity and its functional implications.

Although the organization of cell membranes into lipid rafts has become a key concept in cell biology, how partitioning of membrane components into subdomains is achieved remains an important question.

Using the powerful model system Drosophila melanogaster (fruit fly), DrosAfrica is helping to create an interconnected community of biomedical scientists. DrosAfrica is now aiming at creating African institutes that will allow researchers to run impactful biomedical projects. For this, long term sustainable funding is urgently needed. How DrosAfrica is contributing to shaping research and promoting

Light from a lab’s windows and lamps illuminated the path to the discovery of DNA repair.

Computer-designed organisms — biobots, such as xenobots — are at the intersection of synthetic developmental biology and machine learning. This technology, which enables the evolution of real, living forms to take place in a virtual world, is part of an emerging new research field with applications in biomedicine and engineering, and raises profound philosophical questions. Michael Levin and colleagues

Spotlight on Beth Levine’s contributions to autophagy research and its clinical translation.

Two studies in nematodes revolutionized our understanding of gene regulation by identifying and functionally characterizing the first microRNA, lin-4.

A new study demonstrates that glypicans shield the palmitoleate on WNTs to enable their distribution in tissues.

Roland Wenger highlights discovery of HIFs and recent insights into their differential physiological roles

Ana García-Sáez highlights the continued interest in BCL-2 proteins and their mechanisms

DPPA2 and DPPA4 maintain promoter bivalency and low levels of DNA methylation at certain lineage-specific genes.

Circadian clocks control the function of our immune system, virus replication and the severity of infections. Our daily rhythms also regulate the pharmacokinetics and efficacy of several therapeutics. Consequently, better understanding of the effects of circadian biology on SARS-CoV-2 infection would improve the clinical management of COVID-19. Circadian clocks control our immune system, infections

Vietri et al. show that failure to repair micronuclear membranes is caused by unrestrained activity of ESCRT-III.

Histones serve to both package and organize DNA within the nucleus. In addition to histone post-translational modification and chromatin remodelling complexes, histone variants contribute to the complexity of epigenetic regulation of the genome. Histone variants are characterized by a distinct protein sequence and a selection of designated chaperone systems and chromatin remodelling complexes that

Extracellular vesicles secreted from cells of young donors ameliorate senescence-related damage in cells from old donors

The historical reliance of biological research on the use of animal models has sometimes made it challenging to address questions that are specific to the understanding of human biology and disease. But with the advent of human organoids — which are stem cell-derived 3D culture systems — it is now possible to re-create the architecture and physiology of human organs in remarkable detail. Human organoids

Biomolecular condensation partitions cellular contents and has important roles in stress responses, maintaining homeostasis, development and disease. Many nuclear and cytoplasmic condensates are rich in RNA and RNA-binding proteins (RBPs), which undergo liquid–liquid phase separation (LLPS). Whereas the role of RBPs in condensates has been well studied, less attention has been paid to the contribution

Increased expression of the circular RNA generated by the sulfateless gene (circSfl), and of the protein it encodes, can extend the lifespan of flies.

Complete and accurate DNA replication requires the progression of replication forks through DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent studies have revealed a remarkable plasticity of the replication process in dealing with these obstacles, which includes modulation of replication origin firing, of the architecture of replication forks, and of the functional

The SARS coronavirus 2 (SARS-CoV-2) pandemic is a global challenge, which the scientific community has tackled by mounting extensive global collaborations, combining expertise in diverse areas and applying cutting-edge techniques, to dissect mechanisms underlying coronavirus disease-19 (COVID-19) pathology. The Human Cell Atlas consortium is emerging as an important contributor to furthering this progress

Young and colleagues show that anti-cancer compounds can undergo partitioning into biomolecular condensates, affecting their activity.

The proteins extracellular signal-regulated kinase 1 (ERK1) and ERK2 are the downstream components of a phosphorelay pathway that conveys growth and mitogenic signals largely channelled by the small RAS GTPases. By phosphorylating widely diverse substrates, ERK proteins govern a variety of evolutionarily conserved cellular processes in metazoans, the dysregulation of which contributes to the cause

Human ageing is associated with high susceptibility to disease. Some aspects of ageing can be studied directly in humans and have revealed that ageing is influenced by many factors, including genetics, lifestyle, sex and socio-economic status. But identifying the factors that cause and modulate the ageing process often requires experimental interventions and modelling that can only be performed in

Building a research group in China (when you have not mastered the language) means you face the same problems as elsewhere, with an extra bit of confusion. Running a research group in China with limited knowledge of Chinese is an interesting life experience, Luis Pedro Coelho tells us.

Starting a research group in a developing country can be economically, intellectually and personally challenging, but funding and other opportunities may be broader than they may seem from afar. Selene Fernandez-Valverde recounts her challenges in starting a research group in Mexico.

Mentorship is an important component of academic success. Here, I share my personal experience as a mentee and a mentor from the perspective of a junior principal investigator. Vaishnavi Ananthanarayanan, who is a junior PI at the Indian Institute of Science in Bangalore, India, shares her personal experience as a mentee and a mentor.

A non-catalytic function of PRC1 is required for chromatin interactions that can facilitate developmental gene activation.

Premalignant skin stem cells become dependent on extracellular serine for proliferation, and this metabolic reprogramming inhibits tumour-suppressing cell differentiation.

The coronavirus disease-19 (COVID-19) pandemic underscores the threat posed by newly emerging viruses. Understanding the biology of novel viruses rests in large part on in vitro models that allow viral replication. Human and animal organoids are now proving their value as an experimental virology platform. Hans Clevers discusses the value of organoids as an experimental platform for understanding the

RNA tailing, or the addition of non-templated nucleotides to the 3′ end of RNA, is the most frequent and conserved type of RNA modification. The addition of tails and their composition reflect RNA maturation stages and have important roles in determining the fate of the modified RNAs. Apart from canonical poly(A) polymerases, which add poly(A) tails to mRNAs in a transcription-coupled manner, a family