Mecp2 is a transcriptional repressor
protein that is mutated in
Rett syndrome, a
neurodevelopmental disorder that is the second most common cause of
mental retardation in women. It has been shown that the loss of the
Mecp2 protein in
Rett syndrome cells alters the transcriptional silencing of coding genes and
microRNAs. Herein, we have studied the impact of Mecp2 impairment in a
Rett syndrome mouse model on the global transcriptional patterns of long non-coding RNAs (lncRNAs). Using a microarray platform that assesses 41,232 unique
lncRNA transcripts, we have identified the aberrant
lncRNA transcriptome that is present in the brain of
Rett syndrome mice. The study of the most relevant lncRNAs altered in the assay highlighted the upregulation of the AK081227 and AK087060 transcripts in Mecp2-null mice brains.
Chromatin immunoprecipitation demonstrated the Mecp2 occupancy in the 5'-end genomic loci of the described lncRNAs and its absence in
Rett syndrome mice. Most importantly, we were able to show that the overexpression of AK081227 mediated by the Mecp2 loss was associated with the downregulation of its host coding
protein gene, the
gamma-aminobutyric acid receptor subunit Rho 2 (Gabrr2). Overall, our findings indicate that the transcriptional dysregulation of lncRNAs upon Mecp2 loss contributes to the neurological phenotype of
Rett syndrome and highlights the complex interaction between ncRNAs and coding-RNAs.