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Series GSE78928 Query DataSets for GSE78928
Status Public on Aug 07, 2018
Title Huntingtin aggregation impairs autophagy leading to Argonaute-2 accumulation and global microRNA dysregulation
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Summary Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates resulting in alterations in autophagy. However, the consequences of impaired autophagy on neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation, as well as post-mortem material from patients with Huntington's disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNAinduced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation, but also directly contributes to global alterations of intracellular posttranscriptional networks.
 
Overall design Examination of mRNA sequencing of i) lentiviral mediated overexpression of wtHTT (18Q) and mHTT (66Q) in 293T cells, ii) striatal tissue collected from AAV-wtHTT and AAV-mHTT injected mice and examination of small RNA sequencing from i) lentiviral mediated overexpression of wtHTT (18Q) and mHTT (66Q) in 293T cells and ii) AGO2-RIP and total RNA samples obtained from AAV-wtHTT and AAV-mHTT injected mice.
 
Contributor(s) Pircs K, Petri R, Madsen S, Brattås PL, Vuono R, Ottosson DR, St-Amour I, Hersbach BA, Matusiak-Brückner M, Hult Lundh S, Petersén Å, Déglon N, Hébert SS, Parmar M, Barker RA, Jakobsson J
Citation(s) 30089251
Submission date Mar 07, 2016
Last update date May 15, 2019
Contact name Johan Jakobsson
Organization name Lund University
Lab Molecular Neurogenetics
Street address Sölvegatan 17, building A11
City Lund
ZIP/Postal code 221 84
Country Sweden
 
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (30)
GSM2081311 Sample_KP-RNA-18Q-1
GSM2081312 Sample_KP-RNA-18Q-2
GSM2081313 Sample_KP-RNA-18Q-3
Relations
BioProject PRJNA314448
SRA SRP071197

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE78928_featC.miR.HTT.txt.gz 43.7 Kb (ftp)(http) TXT
GSE78928_featC.polyAinvitrorefseq.txt.gz 2.2 Mb (ftp)(http) TXT
GSE78928_featC.polyAinvivorefseq.txt.gz 2.4 Mb (ftp)(http) TXT
GSE78928_featC.small.rRNA.txt.gz 6.7 Kb (ftp)(http) TXT
GSE78928_featC.small.rep_.txt.gz 41.5 Mb (ftp)(http) TXT
Processed data is available on Series record
Raw data are available in SRA

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