Nucleic Acids Chemistry beyond the Watson-Crick Double Helix (37): The formation of RNA foci in repeat expansion disorders is promoted in molecular crowding conditions

摘要

The expansion of d(GGGGCC) repeats in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). 1 The transcribed r(GGGGCC) repeats form RNA foci by phase transition both in vitro and in cells, which are composed of intermolecular non-canonical G-quadruplex and hairpin structures.2 We have demonstrated that physical properties of nucleic acids in the molecular crowding condition had drastic differences relative to dilute solution.3 It is noteworthy that the formation of RNA foci should be associated with cellular environments.