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Chromatin Isolation by RNA Purification ChIRP
Published on: March 25, 2012
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Antisense RNA controls LRP1 Sense transcript expression through interaction with a chromatin-associated protein,
Yasunari Yamanaka1, Mohammad Ali Faghihi1, Marco Magistri1
1Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Cell Reports
|May 5, 2015
Summary
This study identifies a long non-coding RNA (lncRNA), Lrp1-AS, that regulates low-density lipoprotein receptor-related protein 1 (LRP1) expression. Lrp1-AS upregulation correlates with LRP1 downregulation in Alzheimer's disease brain tissue.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Long non-coding RNAs (lncRNAs) and natural antisense transcripts (NATs) play crucial roles in gene regulation, but their mechanisms are often unclear.
- The function of most NATs in modulating gene expression remains largely unknown.
Purpose of the Study:
- To identify and characterize a novel NAT, Lrp1-AS, involved in the regulation of low-density lipoprotein receptor-related protein 1 (Lrp1).
- To elucidate the molecular mechanism by which Lrp1-AS regulates Lrp1 expression.
- To investigate the potential role of Lrp1-AS and LRP1 in Alzheimer's disease.
Main Methods:
- Identification of Lrp1-AS, a NAT of Lrp1.
- Biochemical assays to determine the interaction between Lrp1-AS and high-mobility group box 2 (Hmgb2).
- Functional studies using short oligonucleotides targeting Lrp1-AS.
- Quantitative RT-PCR analysis of human brain tissue samples from Alzheimer's disease patients and controls.
Main Results:
- Lrp1-AS was identified as a NAT that negatively regulates Lrp1 expression.
- Lrp1-AS directly binds to Hmgb2, inhibiting its activity and thereby enhancing Srebp1a-dependent Lrp1 transcription.
- Targeting Lrp1-AS with oligonucleotides disrupted the Lrp1-AS/Hmgb2 interaction, increased Lrp1 expression by enhancing Hmgb2 activity.
- Quantitative RT-PCR revealed upregulation of LRP1-AS and downregulation of LRP1 in brain tissue from Alzheimer's disease patients compared to controls.
Conclusions:
- A novel regulatory mechanism involving a NAT (Lrp1-AS) and a chromatin-associated protein (Hmgb2) modulating Lrp1 expression has been identified.
- This NAT-protein interaction regulates gene expression in a locus-specific manner.
- The findings suggest a potential role for Lrp1-AS and LRP1 dysregulation in Alzheimer's disease pathogenesis.
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