RRC ID |
58789
|
Author |
Wang X, Zhang X, Dang Y, Li D, Lu G, Chan WY, Leung PCK, Zhao S, Qin Y, Chen ZJ.
|
Title |
Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1.
|
Journal |
Nucleic Acids Res
|
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.
|
Volume |
48(8)
|
Pages |
4480-4491
|
Published |
2020-5-7
|
DOI |
10.1093/nar/gkaa127
|
PII |
5766654
|
PMID |
32112110
|
PMC |
PMC7192606
|
MeSH |
Adult
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Cell Line
DNA Breaks, Double-Stranded
DNA Repair
Down-Regulation
Epigenesis, Genetic
Female
Granulosa Cells / metabolism
Humans
Primary Ovarian Insufficiency / genetics*
Primary Ovarian Insufficiency / metabolism
Promoter Regions, Genetic
RNA, Long Noncoding / metabolism*
RNA, Long Noncoding / physiology
Transcriptional Activation*
Y-Box-Binding Protein 1 / metabolism*
|
IF |
11.502
|
Resource |
Human and Animal Cells |
KGN(RCB1154) |