PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells
Abstract Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic β‐cell development and function in maintaining glucose homeostasis. Poly(A)‐specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet it...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-11-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202407774 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189805168623616 |
|---|---|
| author | Xiaomei Xie Xuexue Chen Chaofan Wang Longjie Sun Weiru Yu Zheng Lv Shuang Tian Xiaohong Yao Fengchao Wang Deqiang Ding Juan Chen Jiali Liu |
| author_facet | Xiaomei Xie Xuexue Chen Chaofan Wang Longjie Sun Weiru Yu Zheng Lv Shuang Tian Xiaohong Yao Fengchao Wang Deqiang Ding Juan Chen Jiali Liu |
| author_sort | Xiaomei Xie |
| collection | DOAJ |
| description | Abstract Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic β‐cell development and function in maintaining glucose homeostasis. Poly(A)‐specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic β cells remains unclear. This study utilizes mice with targeted PARN deficiency in β cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered β‐cell development and insulin sensitivity but reduced glucose‐stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT‐1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN‐deficient β cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract‐binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion. |
| format | Article |
| id | doaj-art-229f94411be64da18e705152d6ec396d |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-229f94411be64da18e705152d6ec396d2025-08-20T02:15:32ZengWileyAdvanced Science2198-38442024-11-011142n/an/a10.1002/advs.202407774PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β CellsXiaomei Xie0Xuexue Chen1Chaofan Wang2Longjie Sun3Weiru Yu4Zheng Lv5Shuang Tian6Xiaohong Yao7Fengchao Wang8Deqiang Ding9Juan Chen10Jiali Liu11State Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaKey Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University Beijing 100190 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaNational Institute of Biological Sciences Beijing 102206 ChinaShanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center Shanghai First Maternity and Infant Hospital Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University Shanghai 200092 ChinaKey Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University Beijing 100190 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaAbstract Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic β‐cell development and function in maintaining glucose homeostasis. Poly(A)‐specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic β cells remains unclear. This study utilizes mice with targeted PARN deficiency in β cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered β‐cell development and insulin sensitivity but reduced glucose‐stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT‐1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN‐deficient β cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract‐binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion.https://doi.org/10.1002/advs.202407774β cellinsulin maturation and secretionRNA binding protein |
| spellingShingle | Xiaomei Xie Xuexue Chen Chaofan Wang Longjie Sun Weiru Yu Zheng Lv Shuang Tian Xiaohong Yao Fengchao Wang Deqiang Ding Juan Chen Jiali Liu PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells Advanced Science β cell insulin maturation and secretion RNA binding protein |
| title | PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells |
| title_full | PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells |
| title_fullStr | PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells |
| title_full_unstemmed | PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells |
| title_short | PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic β Cells |
| title_sort | parn maintains rna stability to regulate insulin maturation and gsis in pancreatic β cells |
| topic | β cell insulin maturation and secretion RNA binding protein |
| url | https://doi.org/10.1002/advs.202407774 |
| work_keys_str_mv | AT xiaomeixie parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT xuexuechen parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT chaofanwang parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT longjiesun parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT weiruyu parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT zhenglv parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT shuangtian parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT xiaohongyao parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT fengchaowang parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT deqiangding parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT juanchen parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells AT jialiliu parnmaintainsrnastabilitytoregulateinsulinmaturationandgsisinpancreaticbcells |