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A long noncoding RNA, LOC157273, is the effector transcript at the chromosome 8p23.1-PPP1R3B metabolic traits and type 2 diabetes risk locus

ABSTRACT: Genome wide association studies (GWAS) identified a chromosome 8 locus associated with fasting glucose (FG), insulin (FI) and lipid levels that is located near PPP1R3B (a gene which encodes the catalytic subunit of a serine/threonine protein phosphatase that promotes hepatic glycogen storage upon insulin signaling). The lead SNP rs4841132 lies in a long non-coding RNA (lncRNA) LOC157273, 175 kb away and is not in linkage disequilibrium with PPP1R3B. Our analysis of the FANTOM consortium data shows LOC157273 is expressed only in hepatocytes. We hypothesized that LOC157273 is the causal candidate that acts upstream of PPP1R3B to regulate FG and FI. Human whole transcriptome sequencing was performed to understand which other genes undergo changes in expression levels upon silencing of LOC157273.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142385 | GEO | 2020/04/01

REPOSITORIES: GEO

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Project description:Background Insulin signaling pathway is conserved from worms to humans. In Drosophila, three insulin-like peptides (dilps) are expressed in the insulin producing cells (IPCs) in the brain. In order to identify target genes of insulin signaling, the IPCs of female flies were destroyed during development by expressing apoptosis inducing factors reaper and head involution defective under control of the promoter region of dilp3. These insulin-deficient flies were analysed using high density microarrays. Results From the genes that appeared to be regulated in the absence of IPCs, the strongest difference was found for a gene involved in carbohydrate metabolism. Sequence analysis revealed that it is an alpha-glucosidase, which is able to break down disaccharides and/or glycogen. Conclusions We could identify an alpha-glucosidase, involved in carbohydrate metabolism, to be strongly affected in the context of decreased insulin signaling. The striking feature of this regulation was not only that it was the highest regulated, but it was the only gene regulated to this degree. Nutrient Conditions and Fly handling Experimental and control female flies were collected after hatching, then kept on fly maintenance food and separated from males after 11 days. After one day of recovery from carbon dioxide treatment, females were put in cages with PBS agar plates and supplied with yeast paste as only food source for 48 hours. Flies were shock frozen in liquid nitrogen and stored at - 80Â°C for further handling. Keywords: IPC knockout, 14 day old female flies, 48h yeast feeding Insulin producing cell deficient flies were compared to control flies. Two independent biological repeats were performed. From the two repeats, 5 chips were hybridised, including dye swap Experimental and control female flies were collected after hatching, then kept on fly maintenance food and separated from males after 11 days. After one day of recovery from carbon dioxide treatment, females were put in cages with PBS agar plates and supplied with yeast paste as only food source for 48 hours. The microarray was scanned 3 times: low scan (suffix _L in data table) with a low amplification / intensity to avoid saturated spots for proper data analysis, high scan (suffix _H in data table) with a high amplification / intensity to detect also weak fluorescent spots which are missed in the low scan and medium scan which lies between high and low intensity and gives additional data points for subsequent calculations. Both copies and all hybridisation repeats were used for normalisation, VALUE therefore has the same value for these copies in all relevant hybridisations. For additional information see publication and web link. Keywords = insulin, aging, longevity, nutrient dependance Lot batch = FP7

Dataset Information

A long noncoding RNA, LOC157273, is the effector transcript at the chromosome 8p23.1-PPP1R3B metabolic traits and type 2 diabetes risk locus

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