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James Olzmann discusses the groundbreaking work of Ron Kopito and colleagues, which demonstrated that a CFTR mutant is ubiquitinated and degraded by the cytosolic 26S proteasome. This discovery contributed to our understanding of ERAD and had important implications for the development of therapeutic agents for cystic fibrosis.
The non-coding RNA 7S inhibits transcription initiation in mitochondria by preventing the RNA polymerase from interacting with promoter DNA and transcription factors.
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.
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.
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.