Preprint: Stress-related lncRNA Hsrω-n amplifies CGG repeat toxicity in Drosophila model of FXTAS
A bioRxiv preprint identifies aberrant expression of the long non-coding RNA Hsrω-n as a contributor to neuronal toxicity in a Drosophila model of fragile X-associated tremor/ataxia syndrome.
A preprint on bioRxiv describes experiments in Drosophila showing that overexpression of the stress-responsive long non-coding RNA (lncRNA) Hsrω-n (heat shock RNA omega-nuclear) contributes to the neuronal toxicity caused by expanded CGG repeats associated with fragile X-associated tremor/ataxia syndrome (FXTAS).
FXTAS is an adult-onset neurodegenerative condition that affects some carriers of premutation alleles in the FMR1 (fragile X messenger ribonucleoprotein 1) gene — defined as approximately 55–200 CGG repeat expansions in the 5′ untranslated region of FMR1. The molecular mechanisms downstream of repeat-driven toxicity remain incompletely understood.
Working in a Drosophila transgenic model carrying expanded CGG repeats sufficient to replicate FXTAS-like cellular stress, the authors found that the repeats led to dominant upregulation of Hsrω-n. Genetic manipulation to reduce Hsrω-n expression partially suppressed the CGG-induced neurotoxic phenotype, implicating this lncRNA as a modifier rather than a bystander of CGG-driven cellular damage.
The findings add lncRNA-mediated stress responses to the mechanistic picture of FXTAS and raise the possibility that Hsrω-n or its mammalian functional equivalents could represent targets for further investigation. The preprint has not yet been peer-reviewed.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Fragile X-associated tremor/ataxia syndrome, often called FXTAS (pronounced "fax-tas"), is a condition that can affect some older adults who carry a particular change — known as a premutation — in a gene called FMR1. People with this premutation have an expanded section of repetitive DNA in the gene; this expansion can sometimes cause problems with movement and thinking as carriers age. Researchers publishing a preliminary study (a preprint, which has not yet been fully reviewed by independent scientists) used fruit flies to investigate how this expanded DNA causes harm to nerve cells. They found that the expanded DNA caused a type of molecule called a long non-coding RNA — a chemical messenger that does not make protein but can still influence how cells work — to become overactive. When the researchers reduced the activity of this molecule in the flies, some of the damage appeared to lessen. The team say this finding may help guide future research into the mechanisms of FXTAS. This is an early-stage laboratory study in flies, not a clinical finding. This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
-
Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-07-16Aberrant expression of stress-related Hsrω-n lncRNA contributes to CGG repeat-mediated toxicity in a Drosophila model of FXTAS