GSE115310 Abnormal RNA stability in amyotrophic lateral sclerosis

Contributors : E M Tank ; C Figueroa-Romero ; L M Hinder ; K Bedi ; H C Archbold ; X Li ; K Weskamp ; N Safren ; X Paez-Colasante ; C Pacut ; S Thumma ; M T Paulsen ; K Guo ; J Hur ; M Ljungman ; E L Feldman ; S J BarmadaSeries Type : OtherOrganism : Homo sapiensAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA binding protein TDP-43. TDP-43 regulatesRNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We used Bru-seq and BruChase-seq to assessgenome-wide RNA stabilityinALS patient-derived cells,demonstratingprofound destabilization of ribosomal and mitochondrial transcripts. This pattern wasrecapitulatedbyTDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in post-mortem samples from ALS and FTD patients. Proteomics and functional studies illustrated corresponding reductionsin mitochondrial components and compensatory increasesin protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, ultimately causing cell death by disrupting energy production and protein synthesis pathways.

Source: GEO: Gene Expression Omnibus - July 25, 2018 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research