Genomic imprinting results in the preferential expression of a gene from either the maternal or paternal allele. Nearly all imprinted domains express non-coding RNAs, including both long and small non-coding RNAs, in a parental biased manner. Yet, the physiological functions and molecular mechanisms of these imprinted transcripts are poorly characterized. Our lab aims to determine the cis- and trans-acting mechanisms of imprinted, non-coding RNAs in the brain.
We have established an in vitro system that enables detection and manipulation of allele-specific expression in neurons. We are currently using this system to (1) identify the neuronal targets of orphan snoRNAs, (2) delineate the neuronal networks regulated by imprinted miRNAs, and (3) determine the mechanisms by which imprinted long non-coding RNAs repress genes in cis.
Imprinted disorders arise from inappropriate genetic alterations within imprinted domains. We have previously shown that targeting an imprinted long non-coding RNA is a viable therapeutic strategy for treatment of an imprinted disorder. In the future, we will perform additional studies to examine the physiological role of imprinted non-coding RNAs during normal and dysregulated neurodevelopment.