Phase separation of RNA-binding proteins in physiology and disease: a thematic series

Coordinating Editors: James Shorter and Paul Fraser

Phase separation of RNA-binding proteins in physiology and disease: a thematic series

The cover image shows LAF-1 droplets assembled on an untreated glass surface. Artwork by Luciana Giono.

Phase separation of RNA-binding proteins in physiology and disease: An introduction to the JBC Reviews thematic series

Abstract
In recent years, there has been a jarring awakening that liquid-liquid phase separation (LLPS) of key protein and nucleic acid scaffolds underpins the biogenesis of diverse membraneless organelles, including P granules and stress granules in the cytoplasm, and, nucleoli and paraspeckles in the nucleus. These biomolecular condensates are proposed to be critical organizers of subcellular biochemistry and to control the flow of information from genotype to phenotype. Despite clear biological utility, LLPS can also have deleterious outcomes. Phase-separated compartments can concentrate specific RNA-binding proteins (RBPs), such as TDP-43 and FUS, that through low-complexity, prion-like domains have an intrinsic tendency to form self-templating fibrils that are closely tied to fatal neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia. This series of reviews illuminates the molecular language underlying membraneless organelle biogenesis, how prion-like domains and post-translational modifications regulate phase behavior, how cells exploit the phase-separation process for adaptive modalities, and how phase separation is corrupted in neurodegenerative diseases. Collectively, these pieces provide a cutting-edge view of our functional and mechanistic understanding of phase separation in physiology and disease.



Reviews in this Series:

  • Edward Gomes, James Shorter
    Preview
  • Titus M. Franzmann, Simon Alberti
    Preview
  • Mario Hofweber, Dorothee Dormann
    Preview
  • Haneul Yoo, Catherine Triandafillou, D. Allan Drummond
    Preview
  • Shana Elbaum-Garfinkle
    Preview


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