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)...

Full description

Bibliographic Details
Main Authors: Miaomiao Wang, Yang Wang, Liu Yang, Xing Du, Qifa Li
Format: Article
Language:English
Published: BMC 2023-10-01
Series:BMC Biology
Subjects:
Online Access:https://doi.org/10.1186/s12915-023-01731-x
_version_ 1827708304273440768
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
work_keys_str_mv AT miaomiaowang nuclearlncrnanorsfreducese2releaseingranulosacellsbyspongingtheendogenoussmallactivatingrnamir339
AT yangwang nuclearlncrnanorsfreducese2releaseingranulosacellsbyspongingtheendogenoussmallactivatingrnamir339
AT liuyang nuclearlncrnanorsfreducese2releaseingranulosacellsbyspongingtheendogenoussmallactivatingrnamir339
AT xingdu nuclearlncrnanorsfreducese2releaseingranulosacellsbyspongingtheendogenoussmallactivatingrnamir339
AT qifali nuclearlncrnanorsfreducese2releaseingranulosacellsbyspongingtheendogenoussmallactivatingrnamir339