Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7.
Details
Serval ID
serval:BIB_CE54623461BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7.
Journal
Nature Structural and Molecular Biology
ISSN
1545-9985 (Electronic)
ISSN-L
1545-9985
Publication state
Published
Issued date
2014
Volume
21
Number
11
Pages
955-961
Language
english
Abstract
What causes the tissue-specific pathology of diseases resulting from mutations in housekeeping genes? Specifically, in spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disorder caused by a CAG-repeat expansion in ATXN7 (which encodes an essential component of the mammalian transcription coactivation complex, STAGA), the factors underlying the characteristic progressive cerebellar and retinal degeneration in patients were unknown. We found that STAGA is required for the transcription initiation of miR-124, which in turn mediates the post-transcriptional cross-talk between lnc-SCA7, a conserved long noncoding RNA, and ATXN7 mRNA. In SCA7, mutations in ATXN7 disrupt these regulatory interactions and result in a neuron-specific increase in ATXN7 expression. Strikingly, in mice this increase is most prominent in the SCA7 disease-relevant tissues, namely the retina and cerebellum. Our results illustrate how noncoding RNA-mediated feedback regulation of a ubiquitously expressed housekeeping gene may contribute to specific neurodegeneration.
Keywords
Animals, Ataxin-7, Cell Line, Tumor, Cerebellum/metabolism, Cerebellum/pathology, Feedback, Physiological, Female, Fibroblasts/metabolism, Fibroblasts/pathology, Gene Expression Profiling, Gene Expression Regulation, Humans, Male, Mice, MicroRNAs/genetics, MicroRNAs/metabolism, Mutation, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Neurons/metabolism, Neurons/pathology, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, RNA, Messenger/genetics, RNA, Messenger/metabolism, Retina/metabolism, Retina/pathology, Signal Transduction, Spinocerebellar Ataxias/genetics, Spinocerebellar Ataxias/metabolism, Transcription Initiation, Genetic
Pubmed
Web of science
Create date
27/10/2014 15:43
Last modification date
20/08/2019 16:48