The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective. Here, we report results from two genome-wide loss-of-function TDP-43 toxicity suppressor screens in yeast. The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43–mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS.
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Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
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Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants
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Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
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Self-citationLong pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
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Cited by
Circular intronic long noncoding RNAs
Zhang, Y., Zhang, X.-O., Chen, T., Xiang, J.-F., Yin, Q.-F., Xing, Y.-H., Zhu, S., Yang, L., & Chen, L.-L. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.017 · Cited by 2,221
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Chen, L.-L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.32 · Cited by 1,743
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS
Yu, C.-H., Davidson, S., Harapas, C. R., Hilton, J. B., Mlodzianoski, M. J., Laohamonthonkul, P., Louis, C., Low, R. R. J., Moecking, J., De Nardo, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.020 · Cited by 1,019
The changing scene of amyotrophic lateral sclerosis
Robberecht, W., & Philips, T. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3430 · Cited by 957
Eukaryotic Stress Granules Are Cleared by Autophagy and Cdc48/VCP Function
Buchan, J. R., Kolaitis, R.-M., Taylor, J. P., & Parker, R. (2013) · Cell · doi:10.1016/j.cell.2013.05.037 · Cited by 737
Metadata
- Authors
- Armakola, M., Higgins, M. J., Figley, M. D., Barmada, S. J., Scarborough, E. A., Diaz, Z., Fang, X., Shorter, J., Krogan, N. J., Finkbeiner, S., Farese, R. V., & Gitler, A. D.
- Venue
- Nature Genetics
- Published
- 2012-10-28
- Volume
- 44
- Issue
- 12
- Pages
- 1302-1309
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2158073956
- Cited by
- 258
- References
- 12
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Armakola, M., Higgins, M. J., Figley, M. D., Barmada, S. J., Scarborough, E. A., Diaz, Z., Fang, X., Shorter, J., Krogan, N. J., Finkbeiner, S., Farese, R. V., & Gitler, A. D. (2012). Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models. Nature Genetics. https://doi.org/10.1038/ng.2434
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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