High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets
Abstract The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11668-w |
| _version_ | 1818210287106392064 |
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| author | Hannah J. MacMillan Yahui Kong Ezequiel Calvo-Roitberg Laura C. Alonso Athma A. Pai |
| author_facet | Hannah J. MacMillan Yahui Kong Ezequiel Calvo-Roitberg Laura C. Alonso Athma A. Pai |
| author_sort | Hannah J. MacMillan |
| collection | DOAJ |
| description | Abstract The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located within ANRIL exon 2 associated with beta cell proliferation. Recent studies have found that expression of circular species of ANRIL is linked to the regulation of cardiovascular phenotypes. Less is known about how the abundance of circular ANRIL may influence T2D phenotypes. Herein, we sequence circular RNA in pancreatic islets to characterize circular isoforms of ANRIL. We identify several consistently expressed circular ANRIL isoforms whose expression is correlated across dozens of individuals and characterize ANRIL splice sites that are commonly involved in back-splicing. We find that samples with the T2D risk allele in ANRIL exon 2 had higher ratios of circular to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL was associated with decreased beta cell proliferation. Our study points to a combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies of the molecular mechanisms by which ANRIL impacts cellular function in pancreatic islets. |
| first_indexed | 2024-12-12T05:14:12Z |
| format | Article |
| id | doaj.art-aee20e476ca048aab9bce02bb6a5a17d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T05:14:12Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-aee20e476ca048aab9bce02bb6a5a17d2022-12-22T00:36:49ZengNature PortfolioScientific Reports2045-23222022-05-0112111510.1038/s41598-022-11668-wHigh-throughput analysis of ANRIL circRNA isoforms in human pancreatic isletsHannah J. MacMillan0Yahui Kong1Ezequiel Calvo-Roitberg2Laura C. Alonso3Athma A. Pai4RNA Therapeutics Institute, University of Massachusetts Chan Medical SchoolUMass Diabetes Center of Excellence, University of Massachusetts Chan Medical SchoolRNA Therapeutics Institute, University of Massachusetts Chan Medical SchoolDivision of Endocrinology, Diabetes and Metabolism, Weill Cornell MedicineRNA Therapeutics Institute, University of Massachusetts Chan Medical SchoolAbstract The antisense non-coding RNA in the INK locus (ANRIL) is a hotspot for genetic variants associated with cardiometabolic disease. We recently found increased ANRIL abundance in human pancreatic islets from donors with certain Type II Diabetes (T2D) risk-SNPs, including a T2D risk-SNP located within ANRIL exon 2 associated with beta cell proliferation. Recent studies have found that expression of circular species of ANRIL is linked to the regulation of cardiovascular phenotypes. Less is known about how the abundance of circular ANRIL may influence T2D phenotypes. Herein, we sequence circular RNA in pancreatic islets to characterize circular isoforms of ANRIL. We identify several consistently expressed circular ANRIL isoforms whose expression is correlated across dozens of individuals and characterize ANRIL splice sites that are commonly involved in back-splicing. We find that samples with the T2D risk allele in ANRIL exon 2 had higher ratios of circular to linear ANRIL compared to protective-allele carriers, and that higher circular:linear ANRIL was associated with decreased beta cell proliferation. Our study points to a combined involvement of both linear and circular ANRIL species in T2D phenotypes and opens the door for future studies of the molecular mechanisms by which ANRIL impacts cellular function in pancreatic islets.https://doi.org/10.1038/s41598-022-11668-w |
| spellingShingle | Hannah J. MacMillan Yahui Kong Ezequiel Calvo-Roitberg Laura C. Alonso Athma A. Pai High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets Scientific Reports |
| title | High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets |
| title_full | High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets |
| title_fullStr | High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets |
| title_full_unstemmed | High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets |
| title_short | High-throughput analysis of ANRIL circRNA isoforms in human pancreatic islets |
| title_sort | high throughput analysis of anril circrna isoforms in human pancreatic islets |
| url | https://doi.org/10.1038/s41598-022-11668-w |
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