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Series GSE55177 Query DataSets for GSE55177
Status Public on Oct 31, 2014
Title Ataxin-2 adapts ribosomal mRNA levels and S6 phosphorylation to nutrient availability, with effects on protein synthesis and growth
Organism Mus musculus
Experiment type Expression profiling by array
Summary Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder, which is caused by an unstable CAG-repeat expansion in the SCA2 gene, that encodes a polyglutamine tract (polyQ-tract) expansion in ataxin-2 protein (ATXN2). The RNA-binding protein ATXN2 interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum or to polysomes. Under cell stress ATXN2 and PABPC1 show redistribution to stress granules where mRNAs are kept away from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates their processing. Here, we investigated Atxn2 knock-out (Atxn2-/-) mouse liver, cerebellum and midbrain regarding their RNA profile, employing oligonucleotide microarrays for screening and RNA deep sequencing for validation. Modest ~1.4-fold upregulations were observed for the level of many mRNAs encoding ribosomal proteins and other translation pathway factors. Quantitative reverse transcriptase PCR and immunoblots in liver tissue confirmed these effects and demonstrated an inverse correlation also with PABPC1 mRNA and protein. ATXN2 deficiency also enhanced phosphorylation of the ribosomal protein S6, while impairing the global protein synthesis rate, suggesting a block between the enhanced translation drive and the impaired execution. Furthermore, ATXN2 overexpression and deficiency retarded cell cycle progression. ATXN2 mRNA levels showed a delayed phasic twofold increase under amino acid and serum starvation, similar to ATXN3, but different from motor neuron disease genes MAPT and SQSTM1. ATXN2 mRNA levels depended particularly on mTOR signalling. Altogether the data implicate ATXN2 in the adaptation of mRNA translation and cell growth to nutrient availability and stress.
 
Overall design Factorial design comparing ataxin-2 knock-out mice with wild type littermates in three different tissues (midbrain, cerebellum, liver) and 3 different ages.
 
Contributor(s) Fittschen M, Lastres-Becker I, Damrath E, Drost J, Klinkenberg M, Heck M, Azizov M, Walter M, Jendrach M, Auburger G
Citation(s) 25721894
Submission date Feb 19, 2014
Last update date Feb 11, 2019
Contact name Michael H. Walter
E-mail michael.walter@agilent.com
Organization name University of Tuebingen
Department Department of Medical Genetics
Lab The Microarray Facility Tübingen
Street address Calwer Str. 7
City Tuebingen
ZIP/Postal code 72076
Country Germany
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (72)
GSM1330956 WT cerebellum 12 month repl. 1
GSM1330957 WT cerebellum 12 month repl. 2
GSM1330958 WT cerebellum 12 month repl. 3
Relations
BioProject PRJNA238815

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Supplementary file Size Download File type/resource
GSE55177_RAW.tar 256.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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