Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339
Abstract Background Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus. Results We identified four nuclear lncRNAs that are presented in granulosa cells (GCs)...
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Format: | Article |
Language: | English |
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BMC
2023-10-01
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Series: | BMC Biology |
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Online Access: | https://doi.org/10.1186/s12915-023-01731-x |
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author | Miaomiao Wang Yang Wang Liu Yang Xing Du Qifa Li |
author_facet | Miaomiao Wang Yang Wang Liu Yang Xing Du Qifa Li |
author_sort | Miaomiao Wang |
collection | DOAJ |
description | Abstract Background Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus. Results We identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis. Conclusions Our findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility. |
first_indexed | 2024-03-10T17:01:47Z |
format | Article |
id | doaj.art-4a43a4e7737f43ff98a1a2f975c6195a |
institution | Directory Open Access Journal |
issn | 1741-7007 |
language | English |
last_indexed | 2024-03-10T17:01:47Z |
publishDate | 2023-10-01 |
publisher | BMC |
record_format | Article |
series | BMC Biology |
spelling | doaj.art-4a43a4e7737f43ff98a1a2f975c6195a2023-11-20T10:55:45ZengBMCBMC Biology1741-70072023-10-0121111310.1186/s12915-023-01731-xNuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339Miaomiao Wang0Yang Wang1Liu Yang2Xing Du3Qifa Li4College of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityAbstract Background Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus. Results We identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis. Conclusions Our findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.https://doi.org/10.1186/s12915-023-01731-xNORSFceRNAmiR-339CYP19A1saRNAE2 release |
spellingShingle | Miaomiao Wang Yang Wang Liu Yang Xing Du Qifa Li Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 BMC Biology NORSF ceRNA miR-339 CYP19A1 saRNA E2 release |
title | Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 |
title_full | Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 |
title_fullStr | Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 |
title_full_unstemmed | Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 |
title_short | Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339 |
title_sort | nuclear lncrna norsf reduces e2 release in granulosa cells by sponging the endogenous small activating rna mir 339 |
topic | NORSF ceRNA miR-339 CYP19A1 saRNA E2 release |
url | https://doi.org/10.1186/s12915-023-01731-x |
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