Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus

作者全名：Chen, Bingnan; Chen, Xuyang; Hu, Ruohan; Li, Hongli; Wang, Min; Zhou, Linwei; Chen, Hao; Wang, Jianqi; Zhang, Hanwen; Zhou, Xiaobo; Zhang, Hua

作者地址：[Chen, Bingnan; Chen, Xuyang; Li, Hongli; Wang, Min; Zhou, Linwei; Chen, Hao; Wang, Jianqi; Zhang, Hanwen; Zhou, Xiaobo; Zhang, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Chen, Bingnan; Chen, Xuyang; Li, Hongli; Wang, Min; Zhou, Linwei; Chen, Hao; Wang, Jianqi; Zhang, Hanwen; Zhou, Xiaobo; Zhang, Hua] Chongqing Med Univ, State Key Lab Maternal & Fetal Med Chongqing Munic, Chongqing, Peoples R China; [Chen, Bingnan; Wang, Min] Chongqing Med Univ, Chongqing Key Lab Translat Med Major Metab Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Hu, Ruohan] Univ Otago, Biomed Sci, Dunedin, New Zealand

通信作者：Zhou, XB; Zhang, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing, Peoples R China.

来源：COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001218690600001

JCR分区：Q2

影响因子：4.4

年份：2024

卷号：23

期号：　

开始页：1298

结束页：1310

文献类型：Article

关键词：Gestational diabetes mellitus; Alternative polyadenylation; Adipose tissue; Transcriptomics; Proteomics; Metabolic disorders; Inflammation

摘要：In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

基金机构：Innovation Project for Doctoral Students at the First Affiliated Hospital of Chongqing Medical University [CYYY-BSYJSCXXM-202210]; National Natural Science Foundation of China [81971406, 82271715]; 111 Project [Yuwaizhuan (2016)32]; Chongqing Science & Technology Commission [cstc2021jcyj-msxmX0213]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ-MSX1679]; Chongqing Municipal Education Commission [KJZD-K202100407]; Chongqing Health Commission and Chongqing Science & Technology Commission [2021MSXM121]

基金资助正文：This work was supported by the Innovation Project for Doctoral Students at the First Affiliated Hospital of Chongqing Medical University (CYYY-BSYJSCXXM-202210) , National Natural Science Foundation of China (81971406, 82271715) , the 111 Project (Yuwaizhuan (2016)32) , Chongqing Science & Technology Commission (cstc2021jcyj-msxmX0213) , Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1679) , Chongqing Municipal Education Commission (KJZD-K202100407) , Chongqing Health Commission and Chongqing Science & Technology Commission (2021MSXM121) .