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
Human and Animal Cells KGN(RCB1154)