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E3 ubiquitin ligases ensure the precise spatiotemporal control of key molecules during important cellular processes. This Review discusses the crucial roles of E3 ligases during early mammalian development and their roles in human disease, and considers how new methods to manipulate the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.
Mammalian RNA polymerase II transcribes protein-coding genes and non-coding transcription units, including long non-coding RNAs (lncRNAs). Studies applying recently developed nascent transcriptomics technology have revealed differences in transcription initiation and termination between lncRNAs and protein-coding genes, bearing relevance to genomic stress and DNA damage.
The majority of macromolecules are transported across the nuclear membrane by the Karyopherin-β (Kap) proteins, comprising importins, exportins and biportins. Unravelling mechanisms and regulation of Kap–cargo interactions is essential for understanding nuclear export and import of proteins and RNA and how this traffic impacts their physiological functions.
Lysine acetyltransferases and lysine deacetylases regulate gene expression and protein function by controlling acetylation and deacetylation of histones and diverse non-histone proteins. The activity of lysine acetyltransferases and lysine deacetylases is regulated by cellular metabolic states, offering the potential for therapeutic modulation through dietary and pharmacological interventions.
X chromosome inactivation in mammals involves chromosome-wide gene silencing at one X chromosome in cells of females, a process that requires complex spatiotemporal regulation. Recent findings provide new insights into the mechanisms and dynamics of X chromosome inactivation and the accompanying 3D reshaping of the chromosome.
Aneuploidy affects organisms from early development through to aging and is a cause of pregnancy loss and cancer. Recent studies have increased our understanding of its mechanisms and how it can be both beneficial and detrimental to cells and organisms, depending on the karyotype and external cues. These insights shed light on its roles in human pathogenesis and on genome evolution.
