title: RNA Granules and Diseases: A Case Study of Stress Granules in ALS and FTLD.
abstract: RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions between proteins with prion-like/low-complexity domains (e.g. FUS and TDP-43). We then explore how dysregulation of RNA granule formation is linked to neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), and discuss possible strategies for therapeutic intervention.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Fan
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. anthony.leung@jhu.edu.
authors.forename: Anthony K L
authors.initials: AK
authors.lastname: Leung
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002451:Cell Compartmentation; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000502:physiology; D020125:Mutation, Missense; D018384:Oxidative Stress; D010442:Peptide Chain Initiation, Translational; D044367:Phase Transition; D011485:Protein Binding; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C000598624:TARDBP protein, human; D012313:RNA
keywords: Low-complexity region; Phase separation; Prion-like domain; RNA granules; Stress granules