Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS

Mercedes Prudencio, Veronique V. Belzil, Ranjan Batra, Christian A. Ross, Tania F. Gendron, Luc J. Pregent, Melissa E. Murray, Karen K. Overstreet, Amelia E. Piazza-Johnston, Pamela Desaro, Kevin F. Bieniek, Michael DeTure, Wing C. Lee, Sherri M. Biendarra, Mary D. Davis, Matthew C. Baker, Ralph B. Perkerson, Marka Van Blitterswijk, Caroline T. Stetler, Rosa RademakersChristopher D. Link, Dennis W. Dickson, Kevin B. Boylan, Hu Li, Leonard Petrucelli

Research output: Contribution to journalArticlepeer-review

255 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1175-1182
Number of pages8
JournalNature Neuroscience
Issue number8
StatePublished - Aug 30 2015
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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