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Repetitive RNA Is Present in Prion-Infected Mouse Brains
Bridges LR.. Preprints.org, 2026-10-02
Topic: Disease mechanisms in lab and animal studies
Scrapie, a prion disease, is usually considered a protein-only infection. However, the repetitive nature of the protein-containing fibrils of prion disease and other neurodegenerations, including Alzheimer’s and Parkinson’s diseases, has led to the hypothesis that RNA, specifically a repetitive RNA, may be present [1–3]. A publicly available RNA-seq dataset from a previous study of mice infected with scrapie [4], was repurposed to test this hypothesis. Using the software superSTR [5], for detecting repetitive elements in RNA-seq data, repeat expansions were found for the known pathogenic motifs, AGC and AAG, along with other motifs, AAAAC, AAAGG, AAGAG and AGAU, all statistically significant compared to controls, with the Mann-Whitney U-test adjusted for multiple testing. They were present at both early and late time points in the disease. Using AlphaFold 3 [6], single- and double-stranded helical structures were predicted for these repetitive RNAs, with the potential to dysregulate protein translation [7] and trigger an interferon type 1 response [8]. Furthermore, the repetitive RNAs were predicted to bind to the prion protein, PrP. The present results suggest a two-component prion, a combined proteinopathy and RNAopathy, with dual toxicity, and raise the possibility of future new diagnostic tests and treatments for prion disease and other neurodegenerations.
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APA 7th
Bridges, L. R. (2026). Repetitive RNA Is Present in Prion-Infected Mouse Brains. Preprints.org. https://doi.org/10.20944/preprints202610.0105.v1
Vancouver
Bridges LR. Repetitive RNA Is Present in Prion-Infected Mouse Brains. Preprints.org. 2026. doi:10.20944/preprints202610.0105.v1.
BibTeX
@article{bridges2026-2036feab,
author = {Bridges, L. R.},
title = {{Repetitive RNA Is Present in Prion-Infected Mouse Brains}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202610.0105.v1},
url = {https://doi.org/10.20944/preprints202610.0105.v1}
}
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Key findings
- Using the software superSTR [5], for detecting repetitive elements in RNA-seq data, repeat expansions were found for the known pathogenic motifs, AGC and AAG, along with other motifs, AAAAC, AAAGG, AAGAG and AGAU, all statistically significant compared to controls, with the Mann-Whitney U-test adjusted for multiple testing.
- The present results suggest a two-component prion, a combined proteinopathy and RNAopathy, with dual toxicity, and raise the possibility of future new diagnostic tests and treatments for prion disease and other neurodegenerations.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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