Cell 211 Review

[Minette Mccandrew]

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Cell death can result from the activation of dedicated programmed cell death machineries or disruption of pro-survival mechanisms. This Review describes the different major mechanisms of cell death and discusses recent insights into their relevance to disease.

This Consensus Statement addresses the definition, nomenclature and classification of long non-coding RNAs, and provides a shared viewpoint on their features and functions. The authors also discuss research challenges and provide recommendations to advance our understanding of long non-coding RNAs.

Are you an early-career researcher who is working with a cool tool or method? Would you like others to learn about it? Let us know! We are introducing Tools of the Trade articles to showcase the role of ECRs in driving technological advancements in molecular cell biology.Email us at n...@nature.com the method/tool you'd like to write about and why it's important.

Nature Reviews Molecular Cell Biology is committed to facilitating training in peer review and to ensuring that everyone involved in our peer-review process is appropriately recognised. We have therefore joined an initiative to allow and encourage established referees to involve one early-career researcher in our peer-review process.

Nicotinamide adenine dinucleotide (NAD+) has essential roles in metabolism and can be readily supplemented, potentially to benefit human health. This Review discusses recent insights into the roles of the microbiome and cellular compartments in regulating NAD+ metabolism, and the promise and pitfalls of NAD+ supplementation.

Tau is a microtubule-binding protein that is expressed primarily in neurons. The abnormal accumulation of tau aggregates in neurons is associated with neurodegenerative diseases, known as tauopathies, such as Alzheimer disease and frontotemporal dementia. This Review discusses recent insights into the diverse cellular functions of tau, the pathology of tau aggregates and the potential for therapeutic interventions.

Recently developed RNA structure profiling methods are transforming our understanding of static and dynamic facets of RNA structures at single-cell and single-molecule resolution. These data have revealed new roles for structures in RNA biogenesis and function, and guide drug design against viral RNAs and for treatment of genetic diseases.

Sphingolipids are a heterogeneous group of lipids with important roles in membrane form and function, cell signalling, and development. This Review discusses the regulation of sphingolipid metabolism at the subcellular and organismal levels and explores the therapeutic potential of targeting sphingolipids in human diseases.

Paul Nurse discusses how a 1971 paper by Culotti and Hartwell inspired him to investigate the cell cycle in fission yeast, and how these genetics studies led to the discovery of cyclin-dependent kinases.

In a recent study, Bong et al. identify a polarized distribution of contact sites between the endoplasmic reticulum and plasma membrane in migrating cells, whereby higher density of contacts in the back of the cells prevents the formation of additional migration fronts.

The subcellular localization of numerous mRNAs has been demonstrated. This Review presents the different means of mRNA localization described and discusses how they can account for the widespread occurrence of this phenomenon.

R-loops and G-quadruplexes are non-canonical nucleic acid structures with known roles in genome organization. Here, Wulfridge and Sarma highlight emerging roles in DNA repair and transcriptional and epigenetic gene regulation.

Several processes of regulated cell death engage or use mitochondria, which are thus central hubs that not only coordinate cell death but also elicit non-lethal signalling mediated by mitochondrial outer membrane permeabilization.

Ferroptosis is a form of cell death that is characterized by morphological abnormalities of mitochondria and the overwhelming peroxidation of phospholipids. Certain tumours are susceptible to ferroptosis, which could be exploited to treat cancers.

Granath-Panelo and Kajimura review emerging evidence of mitochondrial heterogeneity in different contexts and discuss how mitochondrial malleability contributes to cell fate determination and tissue remodelling.

Metastatic colonization involves cancer-cell-intrinsic mechanisms and microenvironmental interactions, and a better understanding of the factors that influence the final, post-extravasation phases is crucial for therapeutically targeting metatstasis.

Mathiowetz and Olzmann review our current understanding of the mechanisms of lipid droplet biogenesis and turnover, the transfer of lipids and metabolites at membrane contact sites, and the role of lipid droplets in regulating fatty acid flux in lipotoxicity and cell death.

In this Review, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive discussion of the molecular regulation of ferroptosis and highlight how this may be potentially leveraged for therapeutic benefit for disease treatment.

In this Review, Andrew Modzelewski, Johnny Gan Chong, Ting Wang and Lin He discuss how sequences introduced by transposon activities provide raw material for genome innovation and document the distinct evolutionary path of each species.

Studying SARS-CoV-2 in organoids. Chen et al. review the emerging roles of complex organoids in the study of SARS-CoV-2 infection, modelling of COVID-19 disease pathology and in drug, antibody and vaccine development.

Legube and Marnef review the association between R-loops and DNA repair. They discuss how R-loops are formed near DNA double-strand breaks (DSBs) and how R-loops affect transcription near DSBs and DSB repair processes.

Karoutas and Akhtar review the roles of the nuclear lamina in chromatin-related functions, including transcription, epigenetic regulation and chromatin architecture, and their abnormalities in diseases and ageing.

This collection highlights recent papers published in Nature Portfolio journals on topics across embryonic development & stem cells, reproductive biology, synthetic tissues & embryo models, clinical & translational research and tissue stem cells.

Intellectual freedom for scientists, unconstrained by commercial interests and direct application, fuels unexpected discoveries. Curiosity-driven, basic science has yielded a deeper understanding of how life forms develop and function in their environment and has had wide implications for health and our planet. Investing in this is vital for scientific progress and worth protecting in a democracy.

We celebrate our 25th anniversary with this Focus & Collection. We not only look back through biological discoveries, but also discuss the roles of cell biologists in sustainability, our ongoing commitments to DEI, and mentoring the next generation.

Shi, Zhou, Xuan, Jiang et al. identify a population of CD8+ T cells that migrate from bone marrow to the small intestine during leukaemogenesis and then traffic back to contribute to anti-leukaemia immune responses during chemotherapy treatment.

Werbowetski-Ogilvie, Taylor and colleagues report a noncanonical role for OTX2 in regulating alternative splicing and controlling a stem cell and pro-tumorigenic splicing program in group 3 medulloblastoma.

Schwab, Rao et al. report that Zeb1 mediates enhanced ferroptosis sensitivity in cancer cells after EMT activation, associated with altered expression of selected lipogenic enzymes and an subsequent increase in the PUFA:MUFA ratio.

Zhou, Jiang, Dai et al report that upon ultraviolet-C radiation, full-length GSDME can induce pyroptosis without cleavage, likely due to conformational change and oxidative oligomerization after increased PARylation and mitochondrial lipid ROS levels.

Cai et al. show that, in lysosomes under hydrostatic pressure in macrophages, lysosomal mechanosensitive channels cause a cation leak. This leads to the inhibition of mTORC1, activation of TFEB/TFE3 and release of monocyte chemoattractant proteins.

The role of RNA in preserving the integrity and dynamics of membrane-bound organelles remains largely unexplored. A study now identifies the Golgi-resident protein GM130 as an RNA-binding protein that scaffolds the Golgi ribbon in a polyadenylated-RNA-dependent manner.

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