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| 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
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| 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.
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| 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.
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| 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 |
Per Brattas |
| Organization name |
Lund University
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| Lab |
Clinical Genomics
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| Street address |
Sölvegatan 17
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| City |
Lund |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
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| Platforms (3) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA314448 |
| SRA |
SRP071197 |
| 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 |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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