A long non-coding RNA transcribed from conserved non-coding sequences contributes to the mouse prolyl oligopeptidase...

Area of Science:

• Genomics
• Molecular Biology
• Gene Regulation

Background:

• Prolyl oligopeptidase (POP) is a key protease in numerous physiological processes.
• The gene regulatory mechanisms governing POP expression remain largely uncharacterized.

Purpose of the Study:

• To identify novel regulatory elements controlling the POP gene.
• To investigate the role of conserved non-coding sequences (CNSs) and associated long non-coding RNAs (lncRNAs) in POP gene regulation.

Main Methods:

• Comparative genomic sequence analysis of mouse and human POP loci.
• Identification and characterization of CNSs and transcribed lncRNAs.
• lncRNA expression analysis and correlation with POP expression.
• lncRNA knockdown and overexpression experiments in primary cells and cell lines.
• Subcellular localization studies of lncRNA.

Main Results:

• Six CNSs were identified near the POP gene, with four transcribing lncRNAs.
• lncPrep+96kb expression correlated with POP expression and was localized to the nucleus and cytoplasm.
• Knockdown of lncPrep+96kb reduced POP expression in both granulosa and hepatic cells.
• Overexpression of lncPrep+96kb increased POP expression specifically in granulosa cells.
• lncPrep+96kb upregulation coincided with POP upregulation during ovarian hormone treatment.

Conclusions:

• lncPrep+96kb is a novel regulator of POP gene expression.
• This lncRNA plays a significant role in POP gene activation, especially within ovarian granulosa cells.
• A new gene activation mechanism involving lncRNAs downstream of the POP gene is proposed.