Review Articles

Mitochondrial respiratory function needs to adapt to the energetic demands of the cell. These adaptive responses encompass transcriptional, translational and post-translational mechanisms that together enable regulation of respiratory chain assembly and mitochondrial membrane remodelling to fine-tune energy generation in accordance with intracellular and extracellular cues.

Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with alternative 3′ untranslated regions; these isoforms modulate protein abundance and functionality, including through subcellular localization of mRNA and translation. APA is modulated by signalling pathways that control co-transcriptional and post-transcriptional processes, and its dysregulation affects cell responses to environmental changes.

Reactive oxygen species (ROS) signalling is crucial in plant responses to abiotic and biotic stresses. This Review discusses our current understanding of ROS regulation and sensing in plants, key regulatory hubs that connect ROS signalling with other stress-response pathways and how ROS signalling could be harnessed to increase plant resilience to environmental stress.

Sumoylation regulates thousands of proteins, many of which are nuclear. Recent studies have implicated sumoylation in liquid–liquid phase separation and assembly of nuclear bodies, and have uncovered its roles in immunity and pluripotency and links to disease, thereby opening new therapeutic avenues.

The Mediator complex is an important regulator of RNA polymerase II. This Review discusses recent structural insights into Mediator function and proposes a model that reconciles contradictory data on whether enhancer–promoter communication during transcription is direct or indirect.

RNA silencing through small RNAs is a major antiviral immunity system in plants. Recent findings are uncovering the roles of RNA silencing in immunity against non-viral pathogens, which is mediated by trans-kingdom RNA movements in vesicles or as extracellular nucleoproteins. RNA silencing also enables the crosstalk between other plant immunity systems.

Homeostasis and function of neurons rely on long-distance, bidirectional microtubule-based transport along the axon, which is driven by both dynein and kinesin motors. How these motors are regulated by a plethora of adaptors and effectors to ensure appropriate and robust distribution of cargos is an area of intense study.

Phosphoinositides are signalling, membrane lipids derived from phosphatidylinositol, whose intracellular distribution and interconversion via phosphoinositide kinases and phosphatases is tightly coupled to membrane dynamics. Accordingly, phosphoinositides are now recognized as key regulators of endocytic and exocytic traffic, the autolysosomal system, and membrane contact site organization and function.

Nuclear receptors are transcription factors that transduce hormonal, nutrient, metabolite and redox signals into regulation of metabolic genes, in particular the transcriptional control of energy metabolism. Accordingly, nuclear receptors have central roles in adapting gene expression to changing energetic demands, thereby maintaining cellular energy homeostasis

Histone H3 Lys9 (H3K9)-methylated heterochromatin ensures transcriptional silencing of repetitive elements and genes, and its deregulation leads to impaired cell and tissue identity, premature aging and cancer. Recent studies in mammals clarified the roles H3K9-specific histone methyltransferases in ensuring transcriptional homeostasis during tissue differentiation.

Abiotic stresses, such as drought, salinity, heat, cold and flooding, have profound effects on plant growth and survival. Adaptation and tolerance to such stresses require sophisticated sensing, signalling and stress response mechanisms. Shroeder and colleagues discuss recent insights into how plant hormones control such responses. Understanding these mechanisms opens opportunities for agricultural applications.

Nuclei are subject to various deformations, being pulled, pushed, squeezed and stretched by a plethora of intracellular and extracellular forces. Recent work is unravelling how nuclei sense and respond to these deformations, including with changes in genome organization and function, cell signalling, and cell mechanics.

Nuclear transcription of a wide variety of RNA species is conducted mainly by three RNA polymerases, which are large and dynamic protein complexes. Recent structural studies have provided important insights into the activities at different transcription stages and the commonalities and differences between these transcription machineries.

RNA–DNA hybrids and R-loop structures are widespread during transcription, replication and DNA repair. R-loops regulate gene expression, but their unfettered accumulation causes genome instability and contributes to neurodegeneration and cancer. Recent mechanistic understanding of R-loop suppression provides therapeutic opportunities to target them.

Apical–basal polarity is essential for epithelial cell form and function. Elucidating how distinct apical and basolateral compartments are established and maintained is essential to better understand the roles of apical–basal cell polarization in morphogenesis and how defects in polarity contribute to diseases such as cancer.

The configuration of microtubule networks is cell type-specific and strongly correlates with cell function and behaviour. The regulation of microtubule nucleation, dynamics and distribution all contribute to the establishment and remodelling of these functionally diverse microtubule architectures.

Mechanical signalling underlies multiple, fundamental biological processes. Mechanical signals can originate from substrate physical properties or shear stresses, and from changes in the physical properties of the cell surface. The mechanisms underlying these two classes of outside-in signalling and their roles in the regulation of intracellular signalling in cell fate and development are becoming increasingly understood.

Pioneer transcription factors activate gene enhancers through their unique ability to initiate opening of inaccessible chromatin. Pioneer factors are crucial for cell fate determination in development and for cellular reprogramming, and their misexpression has major pathological consequences in cancer.

Topoisomerases have essential roles in transcription, DNA replication, chromatin remodelling and, as recently revealed, 3D genome organization. However, topoisomerases also generate DNA–protein crosslinks coupled with DNA breaks, which are increasingly recognized as a source of disease-causing genomic damage.

The regulatory sequences carried by transposable elements (TEs) often recruit the transcription machinery and affect host gene expression. Recent studies have revealed mechanisms by which TEs contribute to transcription regulation, including donation of enhancer and promoter sequences, modification of 3D chromatin architecture, and generation of novel regulatory non-coding RNAs and transcription factors.