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Nuclear pore complexes (NPCs) are large protein assemblies that form channels in the nuclear envelope and constitute major routes for nucleocytoplasmic communication. Insights into the complex structure of NPCs provide the basis for understanding their functions and reveal how the dysfunction of their structural components, nucleoporins, contributes to human disease.
Several years after the characterization of the role of receptor-interacting serine/threonine protein kinase 1 (RIPK1) in cell survival, inflammation and disease, RIPK1 was implicated in the regulation of a newly identified type of cell death known as necroptosis. This Timeline article describes the discoveries that shed light on the roles of RIPK1, RIPK3, mixed-lineage kinase domain-like protein (MLKL) and other regulators of necroptosis in controlling cell fate.
The newly identified SND pathway is an alternative route for the targeting of proteins to the endoplasmic reticulum that functions in parallel to the SRP and GET pathways.
In addition to acetylation, eight types of structurally and functionally different short-chain acylations have recently been identified as important histone Lys modifications: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. These modifications are regulated by enzymatic and metabolic mechanisms and have physiological functions, which include signal-dependent gene activation and metabolic stress.
Histone variants are typically incorporated into chromatin independently of DNA replication and modify chromatin properties. Recent studies have elucidated how particular histone variants are substrates of histone chaperones, chromatin remodellers and histone-modifying enzymes, thereby modifying DNA replication and repair, transcription and chromatin packaging.
Cadherin-based, finger-like cell–cell contacts are shown to serve as instructive structural cues that coordinate motility during collective cell migration.
Human pluripotent stem cells constitute a unique system to study the earliest stages of human embryonic haematopoiesis and the origins of human blood cell diseases, and they are an invaluable tool for the generation of haematopoietic stem and progenitor cell populations for cell-based regenerative therapies.
Edith Heard describes how the discovery of lamina-associated domains changed her thinking about the mechanisms of X-chromosome inactivation and gene regulation.
Job Dekker asserts that cases in which data from microscopy- and 3C-based methods appear discordant about genome organization will provide opportunities to improve our models of chromatin folding.
Genetic variants can produce phenotypic traits through effects on RNA processing, including effects on pre-mRNA splicing, 3′ end formation, and RNA stability, localization, structure and translation efficiency.