Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Mecp2 (methyl CpG binding protein 2) is a transcriptional repressor mutated in Rett syndrome.
• Loss of Mecp2 function alters transcriptional silencing of coding genes and microRNAs.

Purpose of the Study:

• To investigate the impact of Mecp2 impairment on long non-coding RNA (lncRNA) expression in a Rett syndrome mouse model.
• To identify specific lncRNAs dysregulated in the brains of Mecp2-null mice.

Main Methods:

• Microarray analysis of 41,232 unique lncRNA transcripts in mouse brains.
• Chromatin immunoprecipitation to assess Mecp2 binding to lncRNA loci.
• Analysis of the relationship between lncRNA overexpression and host gene downregulation.

Main Results:

• Identified aberrant lncRNA transcriptome in Mecp2-null mouse brains.
• Showed upregulation of AK081227 and AK087060 transcripts in Mecp2-null mice.
• Demonstrated Mecp2 occupancy at the 5' loci of these lncRNAs, which was absent in Mecp2-null mice.
• Found that AK081227 overexpression, due to Mecp2 loss, correlated with downregulation of its host gene, Gabrr2.

Conclusions:

• Transcriptional dysregulation of lncRNAs contributes to the neurological phenotype in Rett syndrome.
• Highlights the intricate interplay between non-coding RNAs (ncRNAs) and coding RNAs in Mecp2-related disorders.