ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/031/SRR21594331/SRR21594331_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/035/SRR21594335/SRR21594335_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/038/SRR21594338/SRR21594338_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/032/SRR21594332/SRR21594332_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/033/SRR21594333/SRR21594333_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/031/SRR21594331/SRR21594331_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/034/SRR21594334/SRR21594334_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/038/SRR21594338/SRR21594338_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/037/SRR21594337/SRR21594337_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/032/SRR21594332/SRR21594332_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/034/SRR21594334/SRR21594334_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/036/SRR21594336/SRR21594336_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/035/SRR21594335/SRR21594335_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/030/SRR21594330/SRR21594330_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/030/SRR21594330/SRR21594330_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/033/SRR21594333/SRR21594333_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/037/SRR21594337/SRR21594337_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR215/036/SRR21594336/SRR21594336_1.fastq.gzprimaryOK200GenomicsM. D. Anderson Cancer Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA880887Homo sapiensxref:PubMed:37329887Obesity has long been considered one of the most important risk factors for a number of cancer types, including breast cancer and remains one the more severe disease concerns. However, the functional importance of noncoding RNA elements remains elusive. Here, we report the upregulation of SNORD46 in obesity serum. The expression status of SNORD46 is correlated with donor’s body mass index (BMI). The expression of SNORD46 in adipocytes was regulated in a CEBP-beta-dependent manner. Mechanically, adipocyte-expressed SNORD46 bound with interleukin-15 (IL-15) in serum, by which Snord46 G11A mutant exhibited enhanced interaction with IL-15. A knockin mouse strain harboring a Snord46 G11A mutation (referred as Snord46mut/mut mice) exhibited obesity and obesity associated complexities compared to wild type or heterozygous littermates. The SNORD46-IL-15 interaction blocked IL-15-dependent non-canonical signaling events, which contained the tyrosine-protein kinase Fer-dependent phosphorylation of platelet glycoprotein 4 (CD36) and monoglyceride lipase (MGLL). Consequently, the obesity-expressed SNORD46 suppressed the IL-15 triggered, Fer-dependent phosphorylation of CD36 and MGLL, leading to inhibited lipase of adipocytes. SNORD46 locked nucleic acids (LNAs) effectively conquered the inhibitory effect of SNORD46 and exhibited anti-obesity effects. Hence, our findings demonstrated the functional importance of snoRNAs in obesity and the efficacy of snoRNA LNAs for antagonizing obesity. Overall design: The CD3-CD56+ NK cells were negatively selected from the peripheral blood mononuclear cells of normal weight donors and obese donors. Then total RNA was profiled after being isolated using QIAzol Lysis Reagent.ENAAI503618, Obesity NOS, Having too much body fat, obesity disease, Adiposity, OBESITY NOS, interleukin-15 receptor ligand, Overweight and obesity, INSDC_feature:ncRNA, Adiposis, Obesity, Lipolyses, multicellular organismal lipid catabolic process, Obese, IL15, unspecified, obesity., IL-15, Interleukin 15, snoRNA, small nucleolar RNA, Obesity [Ambiguous], Obese (finding), OBESITY, multicellular organism lipid catabolic process, Small Nucleolar RNA, obesity disorder, Obesity (disorder)AI503618, Obesity NOS, Having too much body fat, obesity disease, Adiposity, OBESITY NOS, interleukin-15 receptor ligand, Overweight and obesity, INSDC_feature:ncRNA, Adiposis, Obesity, Lipolyses, multicellular organismal lipid catabolic process, Obese, IL15, unspecified, obesity., IL-15, Interleukin 15, snoRNA, small nucleolar RNA, Obesity [Ambiguous], Obese (finding), OBESITY, multicellular organism lipid catabolic process, Small Nucleolar RNA, obesity disorder, Obesity (disorder)falseSnoRNA antagonizes IL-15-mediated lipolysis and promotes obesitySnoRNA antagonizes IL-15-mediated lipolysis and promotes obesity2025-09-242022-10-07PRJNA880887GSE213465960637329887