التفاصيل البيبلوغرافية
| العنوان: |
Transcriptomics-proteomics Integration reveals alternative polyadenylation driving inflammation-related protein translation in patients with diabetic nephropathy |
| المؤلفون: |
Zhao, Tingting, Zhan, Dongdong, Qu, Shuang, Jiang, Song, Gan, Wenhua, Qin, Weisong, Zheng, Chunxia, Cheng, Fang, Lu, Yinghui, Liu, Mingwei, Shi, Jinsong, Liang, Hongwei, Wang, Yi, Qin, Jun, Zen, Ke, Liu, Zhihong |
| المساهمون: |
National Key Research and Development Program, the Project of Jinling Hospital, the Project of Clinical Research Center for Kidney Diseases of Jiangsu Province, Key R&D Projects of Jiangsu Province, National Natural Science Foundation of China |
| المصدر: |
Journal of Translational Medicine ; volume 21, issue 1 ; ISSN 1479-5876 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
General Biochemistry, Genetics and Molecular Biology, General Medicine |
| الوصف: |
Background Diabetic nephropathy (DN) is a complex disease involving the upregulation of many inflammation-related proteins. Alternative polyadenylation (APA), a crucial post-transcriptional regulatory mechanism, has been proven to play vital roles in many inflammatory diseases. However, it is largely unknown whether and how APA exerts function in DN. Methods We performed transcriptomics and proteomics analysis of glomeruli samples isolated from 50 biopsy-proven DN patients and 25 control subjects. DaPars and QAPA algorithms were adopted to identify APA events from RNA-seq data. The qRT-PCR analysis was conducted to verify 3′UTR length alteration. Short and long 3ʹUTRs isoforms were also overexpressed in podocytes under hyperglycemia condition for examining protein expression. Results We detected transcriptome-wide 3′UTR APA events in DN, and found that APA-mediated 3ʹUTR lengthening of genes (APA genes) increased their expression at protein but not mRNA level. Increased protein level of 3′UTR lengthening gene was validated in podocytes under hyperglycemia condition. Pathway enrichment analysis showed that APA genes were enriched in inflammation-related biological processes including endoplasmic reticulum stress pathways, NF-κB signaling and autophagy. Further bioinformatics analysis demonstrated that 3′UTR APA of genes probably altered the binding sites for RNA-binding proteins, thus enhancing protein translation. Conclusion This study revealed for the first time that 3′UTR lengthening of APA genes contributed to the progression of DN by elevating the translation of corresponding proteins, providing new insight and a rich resource for investigating DN mechanisms. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1186/s12967-023-03934-w |
| DOI: |
10.1186/s12967-023-03934-w.pdf |
| DOI: |
10.1186/s12967-023-03934-w/fulltext.html |
| الإتاحة: |
https://doi.org/10.1186/s12967-023-03934-wTest |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.89582F4F |
| قاعدة البيانات: |
BASE |
