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SRX18638722: GSM6808652: Nhr-1 mutant, biological rep 5; Caenorhabditis elegans; RNA-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 24.1M spots, 7.2G bases, 2.2Gb downloads

External Id: GSM6808652_r1
Submitted by: Universidad Internacional de Valencia
Study: Changes in lipid metabolism driven by steroid signalling modulate proteostasis in C. elegans
show Abstracthide Abstract
Alzheimer's, Parkinson's or Huntington's disease can be caused by mutations that enhance protein aggregation, but we still do not know enough about the molecular players of these pathways to develop treatments for these devastating diseases. Here, we screen for mutations that might enhance aggregation and to investigate the mechanisms that protect against dysregulated homeostasis. We report that the protein UNC-1 activates neurohormonal signalling from the sulfotransferase SSU-1 in ASJ sensory/endocrine neurons. This hormone targets the nuclear receptor NHR-1, which acts cell-autonomously in the muscles to protect against aggregation. A second nuclear receptor, DAF-12, functions oppositely to NHR-1 to maintain protein homeostasis. Transcriptomics analyses of unc-1 mutants revealed changes in the expression of genes involved in fat metabolism, suggesting for the first time that fat metabolism changes, controlled by neurohormonal signalling, contribute to protein homeostasis. Furthermore, the enzymes involved in the identified signalling pathway are potential targets for treating neurodegenerative diseases caused by disrupted protein homeostasis. Overall design: Comparative expression analysis of wildtype, unc-1(vlt10), nhr-1(vlt16) and unc-1(vlt10); nhr-1(vlt16) C. elegans young adults carrying a transgene containing a 40-glutamine repeat fused to a yellow fluorescent protein (40Q::YFP). 6 replicates per genotype.
Sample: Nhr-1 mutant, biological rep 5
SAMN32153365 • SRS16083928 • All experiments • All runs
Library:
Name: GSM6808652
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Yound adults were collected in M9 buffer, frozen, thawed and mechanically lysed with 200 mg of glass beads (Sigma-Aldrich-Merck) for 30 sec using a Fastprep shaker apparatus (Thermofisher Scientific, FP120 model) . tRNA was extracted using NZY total RNA isolation kit, Nzytech. Supernatant was recovered from lysate samples by centrifuging extracts at maximum speed for 1 min. The purified RNA was treated with DNAse, quantified and sent for sequencing by Novogene (Cambridge, UK). Library preparation was performed at Novogene facilities (Cambridge, UK). mRNA was enriched using oligo(dT) beads and then fragmented randomly in fragmentation buffer, followed by cDNA synthesis using random hexamers and reverse transcriptase. After first-strand synthesis, a custom second-strand synthesis buffer (Illumina) was added with dNTPs, RNase H and Escherichia coli polymerase I to generate the second strand by nick- translation. To build the final cDNA library, a round of purification, terminal repair, A-tailing, ligation of sequencing adapters, size selection and PCR enrichment were performed. Library concentration was first quantified using a Qubit 2.0 fluorometer (Life Technologies). Insert size was checked on an Agilent 2100 and quantified using quantitative PCR (Q-PCR).
Runs: 1 run, 24.1M spots, 7.2G bases, 2.2Gb
Run# of Spots# of BasesSizePublished
SRR2267641224,089,6217.2G2.2Gb2022-12-12

ID:
25698339

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