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Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1
- Source :
- Nucleic Acids Research
- Publication Year :
- 2020
-
Abstract
- The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA damage repair and promoted apoptosis of GCs. Mechanistically, we discovered that HCP5 stabilized the interaction between YB1 and its partner ILF2, which could mediate YB1 transferring into the nucleus of GCs. HCP5 silencing affected the localization of YB1 into nucleus and reduced the binding of YB1 to the promoter of MSH5 gene, thereby diminishing MSH5 expression. Taken together, we identified that the decreased expression of HCP5 in bPOI contributed to dysfunctional GCs by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.
- Subjects :
- Adult
Transcriptional Activation
endocrine system
DNA Repair
DNA repair
AcademicSubjects/SCI00010
Down-Regulation
Cell Cycle Proteins
Biology
Primary Ovarian Insufficiency
Premature ovarian insufficiency
Cell Line
Epigenesis, Genetic
03 medical and health sciences
0302 clinical medicine
Transcription (biology)
Genetics
RNA and RNA-protein complexes
Gene silencing
Humans
DNA Breaks, Double-Stranded
Epigenetics
Promoter Regions, Genetic
Gene
030304 developmental biology
0303 health sciences
Granulosa Cells
Long non-coding RNA
Cell biology
MSH5
030220 oncology & carcinogenesis
Female
RNA, Long Noncoding
Y-Box-Binding Protein 1
Subjects
Details
- ISSN :
- 13624962
- Volume :
- 48
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Nucleic acids research
- Accession number :
- edsair.doi.dedup.....e104d6671db3f65774ccf45e62d9c41b