The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A natural antisense transcript at the Huntington's disease repeat locus regulates HTT expression
Open accessAbstract
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of huntingtin (HTT). Relatively little attention has been directed to the genomic features of the antisense strand at the HD locus, though the presence of a transcript from this strand has been suggested by a survey of the entire transcriptome and the existence of several EST tags. In this study, we identified huntingtin antisense (HTTAS), a natural antisense transcript at the HD repeat locus that contain the repeat tract. HTTAS is 5' capped, poly (A) tailed and contains three exons, alternatively spliced into HTTAS_v1 (exons 1 and 3) and HTTAS_v2 (exons 2 and 3). Exon 1 includes the repeat. HTTAS_v1 has a weak promoter, and is expressed at low levels in multiple tissue types and throughout the brain. Reporter assays indicate that while efficient promoter activity requires a short repeat, repeat expansion reduces promoter efficiency. Consistent with the reporter assays, levels of HTTAS_v1 are reduced in human HD frontal cortex. In cell systems, overexpression of HTTAS_v1 specifically reduces endogenous HTT transcript levels, while siRNA knockdown of HTTAS_v1 increases HTT transcript levels. Minigene constructs of the HD locus confirm the regulatory effect of HTTAS_v1 on HTT, and demonstrate that the effect is dependent on repeat length and is at least partially Dicer dependent. Together, these findings provide strong evidence for the existence of a gene antisense to HTT, with properties that include regulation of HTT expression.
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Cites
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CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus
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RNA Gain-of-Function in Spinocerebellar Ataxia Type 8
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Cited by
Lagier-Tourenne, C., Baughn, M., Rigo, F., Sun, S., Liu, P., Li, H.-R., Jiang, J., Watt, A. T., Chun, S., Katz, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318835110 · Cited by 561
Targeting long non-coding RNA to therapeutically upregulate gene expression
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The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis
Riva, P., Ratti, A., & Venturin, M. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160622112234 · Cited by 312
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Metadata
- Authors
- Chung, D. W., Rudnicki, D. D., Yu, L., & Margolis, R. L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-13
- Volume
- 20
- Issue
- 17
- Pages
- 3467-3477
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2153992384
- Cited by
- 194
- References
- 7
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chung, D. W., Rudnicki, D. D., Yu, L., & Margolis, R. L. (2011). A natural antisense transcript at the Huntington's disease repeat locus regulates HTT expression. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddr263
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