Optogenetic control of GGGGCC repeat-containing RNA phase transition.

ABSTRACT: The GGGGCC (G₄C₂) hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia. Recent studies have shown that G₄C₂ hexanucleotide repeat-containing RNA transcripts ((G₄C₂)_n RNA) could go through liquid-liquid phase separation to form RNA foci, which may elicit neurodegeneration. However, the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated. Here we introduce an optogenetic control system that can induce the assembly and phase separation of (G₄C₂)_n RNA foci with blue light illumination in human cells, by fusing a specific (G₄

SUBMITTER: Li X 

PROVIDER: S-EPMC11197711 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature