Dysregulated expression of lipid storage and membrane dynamics factors in Tia1 knockout mouse nervous tissue
| Autor: | Georg Auburger, Mekhman Azizov, Melanie Vanessa Heck, Tanja Stehning, Nancy Kedersha, Michael Walter |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
TIA1
RNA processing machinery Cell Cycle Proteins Lipid trafficking Biology Cell cycle Cytoplasmic Granules Perilipin-4 TARDBP Transcriptome Cellular and Molecular Neuroscience Mice Stress granule Contactins Stress Physiological Genetics medicine TIA-1 Animals Homeostasis Genetics(clinical) ddc:610 Motor neuron disease RNA Messenger Genetics (clinical) Cerebellar ataxia Mice Knockout Nervous tissue Gene Expression Profiling Brain Membrane Proteins RNA-Binding Proteins Lipid metabolism Lipid Metabolism Molecular biology T-Cell Intracellular Antigen-1 Gene expression profiling Mice Inbred C57BL medicine.anatomical_structure Spinal Cord Knockout mouse Original Article Apoptosis Regulatory Proteins Carrier Proteins Frontotemporal dementia |
| Zdroj: | Neurogenetics |
| ISSN: | 1364-6753 1364-6745 |
| Popis: | During cell stress, the transcription and translation of immediate early genes are prioritized, while most other messenger RNAs (mRNAs) are stored away in stress granules or degraded in processing bodies (P-bodies). TIA-1 is an mRNA-binding protein that needs to translocate from the nucleus to seed the formation of stress granules in the cytoplasm. Because other stress granule components such as TDP-43, FUS, ATXN2, SMN, MAPT, HNRNPA2B1, and HNRNPA1 are crucial for the motor neuron diseases amyotrophic lateral sclerosis (ALS)/spinal muscular atrophy (SMA) and for the frontotemporal dementia (FTD), here we studied mouse nervous tissue to identify mRNAs with selective dependence on Tia1 deletion. Transcriptome profiling with oligonucleotide microarrays in comparison of spinal cord and cerebellum, together with independent validation in quantitative reverse transcriptase PCR and immunoblots demonstrated several strong and consistent dysregulations. In agreement with previously reported TIA1 knock down effects, cell cycle and apoptosis regulators were affected markedly with expression changes up to +2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb vs. decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong expression alterations were detected for fat storage and membrane trafficking factors, with prominent +3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and Pnpla2 vs. a −2.4-fold downregulation of Cntn4 transcript, encoding an axonal membrane adhesion factor with established haploinsufficiency. In comparison, subtle effects on the RNA processing machinery included up to 1.2-fold upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2 led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid homeostasis factors in the brain, similar to the fasting effect. Electronic supplementary material The online version of this article (doi:10.1007/s10048-014-0397-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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