{"doi":"10.3389/fgene.2020.00615","title":"A Long Non-coding RNA, LOC157273, Is an Effector Transcript at the Chromosome 8p23.1-PPP1R3B Metabolic Traits and Type 2 Diabetes Risk Locus","abstract":"Aims: Causal transcripts at genomic loci associated with type 2 diabetes are mostly unknown. The chr8p23.1 variant rs4841132, associated with an insulin resistant diabetes risk phenotype, lies in the second exon of a long non-coding RNA (lncRNA) gene, LOC157273, located 175 kilobases from PPP1R3B, which encodes a key protein regulating insulin-mediated hepatic glycogen storage in humans. We hypothesized that LOC157273 regulates expression of PPP1R3B in human hepatocytes. Methods: We tested our hypothesis using Stellaris fluorescent in-situ hybridization to assess subcellular localization of LOC157273; siRNA knockdown of LOC157273, followed by RT-PCR to quantify LOC157273 and PPP1R3B expression; RNA-seq to quantify the whole-transcriptome gene expression response to LOC157273 knockdown and an insulin-stimulated assay to measure hepatocyte glycogen deposition before and after knockdown. Results: We found that siRNA knockdown decreased LOC157273 transcript levels by approximately 80%, increased PPP1R3B mRNA levels by 1.7-fold and increased glycogen deposition by >50% in primary human hepatocytes. An A/G heterozygous carrier (vs. three G/G carriers) had reduced LOC157273 abundance due to reduced transcription of the A allele and increased PPP1R3B expression and glycogen deposition. Conclusion: We show that the lncRNA LOC157273 is a negative regulator of PPP1R3B expression and glycogen deposition in human hepatocytes and the causal transcript at an insulin resistant type 2 diabetes risk locus.","journal":"Frontiers in Genetics","year":2020,"id":76888,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9399,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400513,"name":"Anton Scott Goustin","orcid":"0000-0002-4483-5101","position":1,"is_corresponding":false},{"id":400514,"name":"Erica L. Kleinbrink","orcid":"0000-0002-8565-207X","position":2,"is_corresponding":false},{"id":401286,"name":"Pattaraporn Thepsuwan","orcid":null,"position":3,"is_corresponding":false},{"id":400515,"name":"Juan Cai","orcid":"0000-0001-7996-2525","position":4,"is_corresponding":false},{"id":400516,"name":"Donghong Ju","orcid":"0000-0003-3664-859X","position":5,"is_corresponding":false},{"id":263594,"name":"Aaron Leong","orcid":"0000-0002-3248-9547","position":6,"is_corresponding":false},{"id":7372,"name":"Miriam S. Udler","orcid":"0000-0003-3824-9162","position":7,"is_corresponding":false},{"id":401287,"name":"James Bentley Brown","orcid":null,"position":8,"is_corresponding":false},{"id":270034,"name":"Mark O. Goodarzi","orcid":"0000-0001-6364-5103","position":9,"is_corresponding":false},{"id":11276,"name":"Jerome I. Rotter","orcid":"0000-0001-7191-1723","position":10,"is_corresponding":false},{"id":16112,"name":"Robert Sladek","orcid":"0000-0002-2730-1204","position":11,"is_corresponding":false},{"id":1092,"name":"James B. Meigs","orcid":"0000-0002-2439-2657","position":12,"is_corresponding":false},{"id":44602,"name":"Leonard Lipovich","orcid":"0000-0002-0531-3570","position":13,"is_corresponding":false},{"id":16116,"name":"Alisa K. Manning","orcid":"0000-0003-0247-902X","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:48:27.511277Z","pmid":"32754192","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}