2017.10.30 RNA phase transitions in neurodegenerative diseases

2019-07-07 00:50:11 1



    目:RNA phase transitions in neurodegenerative diseases

报告人Dr. Ankur JAIN

Damon Runyon Postdoctoral Fellowship Award

The Ronald D. Vale Lab

Department of Cellular and Molecular Pharmacology

University of California San Francisco



主持人:齐志 研究员

摘 要:

Several neurological and neuromuscular diseases are caused by expansion of short microsatellite repeats. Examples include Huntington disease (CAG expansion), muscular dystrophy (CTG expansion) and some forms of amyotrophic lateral sclerosis (GGGGCC expansion). Two characteristic pathological feature of these diseases are: (1) The RNA transcript with repeats accumulates in the nuclei as aberrant “RNA foci”. (2) RNA foci, as well as disease symptoms, only appear when the number of repeats exceeds a critical threshold. The molecular mechanisms underlying these features were not known. We identified that RNA foci result from sol-to-gel phase transition of the repeat-containing RNA. Phase transitions are mediated by multivalent intermolecular base-pairing between the RNA: increase in the number of repeats corresponds to an increased valency for intermolecular hybridization. Compounds that disrupt base-pairing interactions disrupt RNA foci in patient-derived cells and offer a potential route to therapeutics. Analogous to protein aggregation disorders, we propose that sequence-specific gelation of RNAs could be a contributing factor to neurological disease.


Jain A and Vale R, “RNA phase transitions in repeat expansion disorders”, Nature546, 243-247 (2017)

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