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TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD
Open accessAbstract
Mechanistic surprise in ALS-FTD: Intense efforts have focused on identifying therapeutic targets for misfolded proteins that cause amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). Ling et al. show that the main culprit of proteinopathy, TDP-43, acts as a splicing suppressor of nonconserved cryptic exons. These exons often disrupt messenger RNA translation and promote nonsense-mediated decay. When TDP-43 was depleted in cells, a set of nonconserved cryptic exons spliced into target RNAs, leading to down-regulation of corresponding proteins critical for cellular function. Repression of cryptic exons prevented cell death in TDP-43–null cells. Because brains of ALS-FTD cases showed evidence of missplicing of cryptic exons, failure in these regions may underlie TDP-43 proteinopathy. Science , this issue p. 650
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Metadata
- Authors
- Ling, J. P., Pletnikova, O., Troncoso, J. C., & Wong, P. C.
- Venue
- Science
- Published
- 2015-08-07
- Volume
- 349
- Issue
- 6248
- Pages
- 650-655
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1904847174
- Cited by
- 688
- References
- 11
- FWCI
- 23.08
- Type
- journal article
- Language
- en
- Open access
- green
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