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Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1

Authors :
Peter C.K. Leung
Duan Li
Xiaoyan Wang
Yujie Dang
Shidou Zhao
Xinyue Zhang
Wai-Yee Chan
Zi-Jiang Chen
Yingying Qin
Gang Lu
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.

Details

ISSN :
13624962
Volume :
48
Issue :
8
Database :
OpenAIRE
Journal :
Nucleic acids research
Accession number :
edsair.doi.dedup.....e104d6671db3f65774ccf45e62d9c41b