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42/100

✓ Peer-reviewed alzhub usefulness score 42 out of 100. Lewy body dementia

Topic: Brain proteins, microglia and lab models

Nonsense mutations generate premature termination codons (PTCs) that are responsible for 11% of genetic disease alleles. The arginine (Arg, CGA) to stop (UGA) mutation is the most common PTC. Humans encode >600 transfer RNA (tRNA) genes with many identical and similar copies. We developed a dual fluorescent reporter to quantify PTC readthrough in live cells and found single nucleotide mutations of human tRNAArg gene variants enabled differential nonsense suppression that depended on the tRNA sequence and the cell type. We investigated G36A variants of all six human tRNAArgUCG isodecoders, and only the TCG-6-1 tRNA, where G36A occurs in 0.01% of human genomes, was unable to translate nonsense codons. With tRNA sequencing, we showed that a suppressor tRNA derived from the TCG-3-1 gene was expressed 2.1-fold higher and generated 1.8-fold more nonsense suppression than a tRNA derived from the TCG-4-1 gene. In a neuroblastoma model of frontotemporal dementia, we observed >70% readthrough of progranulin R493X with a suppressor tRNA that represented 5%-18% of the total tRNAArg pool. The tRNAs outperformed aminoglycoside-induced nonsense suppression in efficacy, tolerability to the cells, and translation fidelity according to mass spectrometry. Our studies show that human nonsense suppressor tRNAs can correct genetic defects that cause disease.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Beharry, A., Ward, C., Moore, H., Hoffman, K. S., Chan, P. P., Lowe, T. M., et al. (2025). High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaf730

Vancouver

Beharry A, Ward C, Moore H, Hoffman KS, Chan PP, Lowe TM, et al. High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs. Nucleic Acids Research. 2025. doi:10.1093/nar/gkaf730. PMID: 40794874.

BibTeX

@article{beharry2025-40794874,
  author  = {Beharry, Aruun and Ward, Cian and Moore, Henry and Hoffman, Kyle S. and Chan, Patricia P. and Lowe, Todd M. and O’Donoghue, Patrick},
  title   = {{High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs}},
  journal = {Nucleic Acids Research},
  year    = {2025},
  doi     = {10.1093/nar/gkaf730},
  pmid    = {40794874},
  url     = {https://doi.org/10.1093/nar/gkaf730}
}

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.

Key findings

With tRNA sequencing, we showed that a suppressor tRNA derived from the TCG-3-1 gene was expressed 2.1-fold higher and generated 1.8-fold more nonsense suppression than a tRNA derived from the TCG-4-1 gene.
In a neuroblastoma model of frontotemporal dementia, we observed >70% readthrough of progranulin R493X with a suppressor tRNA that represented 5%-18% of the total tRNAArg pool.

Why it matters

In a neuroblastoma model of frontotemporal dementia, this study observed over 70% readthrough of progranulin R493X using a suppressor tRNA. This is a cell model, so it is early and preliminary and does not yet show a treatment for patients.

Study details

Effect size0.01%
Evidence strengthLow

How this study scored 42/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Nucleic Acids Research)
Journal's citation record	4 / 4	Nucleic Acids Research: journal h-index 869 (OpenAlex, 2026-10-29)
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	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	4 / 5	2025 — within 3 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	2 / 3	Effect reported as a number, without an interval or test
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	2 / 7	Cited 5 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	1.7 citations a year over 3 year(s) since 2025
Impact for its field and year	2 / 6	Cited 1.3× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	1 / 4	Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Patrick O’Donoghue: h-index 34 (OpenAlex, whole career)
Institution's track record	1 / 3	University of California, Santa Cruz: institution h-index 1,098 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 3 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 40794874)
Free to read	2 / 2	Free to read
Total	42 / 100	—

What each of these 20 components measures, and what this score is not →

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