ArticleNeurobiology of disease2021
Distinct Poly(A) nucleases have differential impact on sut-2 dependent tauopathy phenotypes.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Riboregulation: a non-canonical tau function.Molecular neurodegeneration · 2026Review
- Loss of SMARCAD1 Mitigates Tauopathy.Aging cell · 2026Article
- Decoding the functions of nuclear speckles in neurodegeneration.Trends in neurosciences · 2026Review
- Long-read sequencing-based analyses of the adult Drosophila brain transcriptome in physiological and pathological settings.BMC genomics · 2025Article
- Tri-snRNP activity modulates tauopathy phenotypes.NAR molecular medicine · 2025Article
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- Endoplasmic reticulum unfolded protein response transcriptional targets of XBP-1s mediate rescue from tauopathy.Communications biology · 2024Article
- TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy.bioRxiv : the preprint server for biology · 2024Article
- Simple model systems reveal conserved mechanisms of Alzheimer's disease and related tauopathies.Molecular neurodegeneration · 2023Review
- Tau-RNA complexes inhibit microtubule polymerization and drive disease-relevant conformation change.Brain : a journal of neurology · 2023Article
- Sut-6/NIPP1 modulates tau toxicity.Human molecular genetics · 2023Article
- SPOP loss of function protects against tauopathy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Loss of aly/ALYREF suppresses toxicity in both tau and TDP-43 models of neurodegeneration.GeroScience · 2022Article
- TDP-43 promotes tau accumulation and selective neurotoxicity in bigenic Caenorhabditis elegans.Disease models & mechanisms · 2022Article
- Modeling Alzheimer's Disease inBiomedicines · 2022Review
- Pathological tau drives ectopic nuclear speckle scaffold protein SRRM2 accumulation in neuron cytoplasm in Alzheimer's disease.Acta neuropathologica communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Aging drives pathological accumulation of proteins such as tau, causing neurodegenerative dementia disorders like Alzheimer's disease. Previously we showed loss of function mutations in the gene encoding the poly(A) RNA binding protein SUT-2/MSUT2 suppress tau-mediated neurotoxicity in C. elegans neurons, cultured human cells, and mouse brain, while loss of PABPN1 had the opposite effect (Wheeler et al., 2019). Here we found that blocking poly(A) tail extension with cordycepin exacerbates tauopathy in cultured human cells, which is rescued by MSUT2 knockdown. To further investigate the molecular mechanisms of poly(A) RNA-mediated tauopathy suppression, we examined whether genes encoding poly(A) nucleases also modulated tauopathy in a C. elegans tauopathy model. We found that loss of function mutations in C. elegans ccr-4 and panl-2 genes enhanced tauopathy phenotypes in tau transgenic C. elegans while loss of parn-2 partially suppressed tauopathy. In addition, loss of parn-1 blocked tauopathy suppression by loss of parn-2. Epistasis analysis showed that sut-2 loss of function suppressed the tauopathy enhancement caused by loss of ccr-4 and SUT-2 overexpression exacerbated tauopathy even in the presence of parn-2 loss of function in tau transgenic C. elegans. Thus sut-2 modulation of tauopathy is epistatic to ccr-4 and parn-2. We found that human deadenylases do not colocalize with human MSUT2 in nuclear speckles; however, expression levels of TOE1, the homolog of parn-2, correlated with that of MSUT2 in post-mortem Alzheimer's disease patient brains. Alzheimer's disease patients with low TOE1 levels exhibited significantly increased pathological tau deposition and loss of NeuN staining. Taken together, this work suggests suppressing tauopathy cannot be accomplished by simply extending poly(A) tails, but rather a more complex relationship exists between tau, sut-2/MSUT2 function, and control of poly(A) RNA metabolism, and that parn-2/TOE1 may be altered in tauopathy in a similar way.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.