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DOI | 10.1038/s41467-018-07082-4 |
Abnormal RNA stability in amyotrophic lateral sclerosis | |
Tank, E. M.1; Figueroa-Romero, C.1; Hinder, L. M.1; Bed, K.2; Archbold, H. C.1; Li, X.1; Weskamp, K.1; Safren, N.1; Paez-Colasante, X.1; Pacut, C.1; Thumma, S.1; Paulsen, M. T.2; Guo, K.3; Hur, J.3; Ljungman, M.2,4; Feldman, E. L.1,4,5; Barmada, S. J.1,4,5 | |
2018-07-20 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA-binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in postmortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000439297100004 |
WOS关键词 | STRESS GRANULE DYNAMICS ; FRONTOTEMPORAL LOBAR DEGENERATION ; MESSENGER-RNA ; REPEAT EXPANSION ; PHASE-SEPARATION ; OXIDATIVE STRESS ; NUCLEOCYTOPLASMIC TRANSPORT ; CYTOPLASMIC MISLOCALIZATION ; MITOCHONDRIAL MORPHOLOGY ; HEXANUCLEOTIDE REPEAT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204088 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Michigan, Dept Neurol, Med Sch, Ann Arbor, MI 48109 USA; 2.Univ Michigan, Dept Radiat Oncol, Med Sch, Ann Arbor, MI 48109 USA; 3.Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND 58202 USA; 4.Univ Michigan, Cellular & Mol Biol Program, Med Sch, Ann Arbor, MI 48109 USA; 5.Univ Michigan, Med Sch, Neurosci Grad Program, Ann Arbor, MI 48109 USA |
推荐引用方式 GB/T 7714 | Tank, E. M.,Figueroa-Romero, C.,Hinder, L. M.,et al. Abnormal RNA stability in amyotrophic lateral sclerosis[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Tank, E. M..,Figueroa-Romero, C..,Hinder, L. M..,Bed, K..,Archbold, H. C..,...&Barmada, S. J..(2018).Abnormal RNA stability in amyotrophic lateral sclerosis.NATURE COMMUNICATIONS,9. |
MLA | Tank, E. M.,et al."Abnormal RNA stability in amyotrophic lateral sclerosis".NATURE COMMUNICATIONS 9(2018). |
条目包含的文件 | 条目无相关文件。 |
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