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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.
Heterochromatin DNA is heavily methylated yet also inaccessible. Olivier Mathieu describes the work that revealed how DNA methyltransferases access heterochromatin.
The transcription factor c-Maf is required for the specification of liver sinusoids and for the maintenance of a specialized sinusoidal network necessary for sustaining hepatocyte function.
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.
Arnold et al. document an alternative tricarboxylic acid cycle that takes place between the mitochondria and the cytosol and that can be adopted in specific cell states.
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.