Gene expression changes in cervical motor neuron transcriptomes after loss of Hox5 transcription factors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA574474 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10192852_1.fastq.gz | Fastqsanger.gz | |||
| SRR10192852_2.fastq.gz | Fastqsanger.gz | |||
| SRR10192853_1.fastq.gz | Fastqsanger.gz | |||
| SRR10192853_2.fastq.gz | Fastqsanger.gz | |||
| SRR10192854_1.fastq.gz | Fastqsanger.gz |
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Project description:The goal of this study was to identify potential Hox5 target genes in cervical motor neurons (C3-C6) using unbiased genomic screens (RNA-seq). We examined expression changes independently of motor neuron cell death by deleting the pro-apoptotic gene Bax in both control and experimental mice.
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Project description:CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1K/K) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1K/K mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53. RNA was extracted from spinal cord of 3 Clp1 knock-out mice and 3 wild type mice (15 days old, male, all samples age and sex matched) and submitted to differential splicing analysis using Affymetrix Exon microarrays. Differential splicing analysis was performed between the Clp1 KO and WT samles employing a custom CDF, that was based on a complete re-alignment of oligonucleotide probes to the genome and transcriptome (Ensembl 52, ASTD 1.1; further information on http://bioinfo.i-med.ac.at).
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