Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS
| Autor: | Christian A. Ross, Mary D. Davis, Sherri M. Biendarra, Marka van Blitterswijk, Mercedes Prudencio, Ralph B. Perkerson, Amelia E Piazza-Johnston, Caroline Stetler, Ranjan Batra, Kevin F. Bieniek, Karen Overstreet, Rosa Rademakers, Kevin B. Boylan, Leonard Petrucelli, Hu Li, Matt Baker, Christopher D. Link, Luc Pregent, Michael DeTure, Melissa E. Murray, Tania F. Gendron, Pamela Desaro, Veronique V. Belzil, Wing C. Lee, Dennis W. Dickson |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Polyadenylation Biology Transcriptome 03 medical and health sciences 0302 clinical medicine C9orf72 Cerebellum parasitic diseases medicine Humans Amyotrophic lateral sclerosis Genetic Association Studies 030304 developmental biology Aged Regulation of gene expression Genetics 0303 health sciences C9orf72 Protein Heterogeneous-Nuclear Ribonucleoprotein Group F-H Sequence Analysis RNA General Neuroscience Alternative splicing Amyotrophic Lateral Sclerosis C9orf72 Gene RNA Proteins Middle Aged medicine.disease Frontal Lobe Alternative Splicing Gene Expression Regulation Human medicine Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS subjects (8,224 AS and 1,437 APA), including changes in ALS-associated genes (for example, ATXN2 and FUS), and in subjects with sporadic ALS (sALS; 2,229 AS and 716 APA). Furthermore, heterogeneous nuclear ribonucleoprotein H (hnRNPH) and other RNA-binding proteins are predicted to be potential regulators of cassette exon AS events in both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. |
| Databáze: | OpenAIRE |
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