The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis
Abstract Acute kidney injury (AKI) is a serious clinical condition whose underlying mechanisms remain unclear. Here we identify a long non-coding RNA, RSDR, as a critical regulator of renal protection in AKI. RSDR interacts with the RNA-binding protein hnRNPK, forming a positive feedback loop that e...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62433-2 |
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| author | Bojun Li Fangyou Lin Baofeng Song ShangTing Han Zehua Ye Yushi Sun Peihan Wang Yuqi Xia Weimin Yu Xiangjun Zhou Fan Cheng |
| author_facet | Bojun Li Fangyou Lin Baofeng Song ShangTing Han Zehua Ye Yushi Sun Peihan Wang Yuqi Xia Weimin Yu Xiangjun Zhou Fan Cheng |
| author_sort | Bojun Li |
| collection | DOAJ |
| description | Abstract Acute kidney injury (AKI) is a serious clinical condition whose underlying mechanisms remain unclear. Here we identify a long non-coding RNA, RSDR, as a critical regulator of renal protection in AKI. RSDR interacts with the RNA-binding protein hnRNPK, forming a positive feedback loop that enhances the transcription of DHODH, a key ferroptosis-suppressing gene. Mechanistically, RSDR promotes the nuclear retention of hnRNPK and facilitates epigenetic activation of DHODH, thereby limiting ferroptosis in renal tubular epithelial cells. In vivo overexpression of RSDR attenuates ferroptosis and preserves renal function in male mice during AKI. Clinically, urinary RSDR levels are significantly reduced in patients with AKI, and machine learning analysis suggests potential utility in disease detection. These findings highlight RSDR as a central regulator of ferroptosis and provide mechanistic insights into lncRNA-mediated tubular protection in AKI. |
| format | Article |
| id | doaj-art-bbe58b2de9104e4da8df2684d6dee825 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bbe58b2de9104e4da8df2684d6dee8252025-08-20T03:43:10ZengNature PortfolioNature Communications2041-17232025-08-0116112010.1038/s41467-025-62433-2The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosisBojun Li0Fangyou Lin1Baofeng Song2ShangTing Han3Zehua Ye4Yushi Sun5Peihan Wang6Yuqi Xia7Weimin Yu8Xiangjun Zhou9Fan Cheng10Department of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityAbstract Acute kidney injury (AKI) is a serious clinical condition whose underlying mechanisms remain unclear. Here we identify a long non-coding RNA, RSDR, as a critical regulator of renal protection in AKI. RSDR interacts with the RNA-binding protein hnRNPK, forming a positive feedback loop that enhances the transcription of DHODH, a key ferroptosis-suppressing gene. Mechanistically, RSDR promotes the nuclear retention of hnRNPK and facilitates epigenetic activation of DHODH, thereby limiting ferroptosis in renal tubular epithelial cells. In vivo overexpression of RSDR attenuates ferroptosis and preserves renal function in male mice during AKI. Clinically, urinary RSDR levels are significantly reduced in patients with AKI, and machine learning analysis suggests potential utility in disease detection. These findings highlight RSDR as a central regulator of ferroptosis and provide mechanistic insights into lncRNA-mediated tubular protection in AKI.https://doi.org/10.1038/s41467-025-62433-2 |
| spellingShingle | Bojun Li Fangyou Lin Baofeng Song ShangTing Han Zehua Ye Yushi Sun Peihan Wang Yuqi Xia Weimin Yu Xiangjun Zhou Fan Cheng The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis Nature Communications |
| title | The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis |
| title_full | The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis |
| title_fullStr | The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis |
| title_full_unstemmed | The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis |
| title_short | The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis |
| title_sort | long non coding rna rsdr protects against acute kidney injury in mice by interacting with hnrnpk to regulate dhodh mediated ferroptosis |
| url | https://doi.org/10.1038/s41467-025-62433-2 |
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