Author: cjt15104

First Place Winner, Ph.D. Students Poster Presentations

“Genomic Imprinting – From Biology to Disease 2020” by Dea Gorka

Virtual Seminar Cambridge, UK
September 28 – October 1, 2020

The work is about gaining a better understanding of the function of UBE3A-ATS, a long non-coding RNA, that leads to the silencing of UBE3A in order to learn more about Angelman syndrome and discover novel therapeutic options for these patients.

More specifically: Angelman Syndrome is caused by loss of function from the maternally inherited allele of UBE3A. In most cell types, UBE3A is only expressed from the maternally-inherited allele. Thus, loss of function from the maternal allele leads to nearly complete loss of UBE3A RNA and protein. Imprinted (maternal-only) expression of UBE3A occurs because the paternal allele of UBE3A is silenced by a long non-coding antisense RNA, termed UBE3A-ATS.

In non-neuronal cell types, transcription of UBE3A-ATS terminates before it silences UBE3A. However, in mature neurons, the transcription extends to the UBE3A locus and silences paternal UBE3A. The mechanism restricting UBE3A imprinting to neurons is not well understood.

Our goal is to identify the underlying mechanism of how the neuron specific UBE3A-ATS transcript is regulated in a cell-type specific manner using AS patient derived induced pluripotent stem cells (iPSCs) and their neuronal derivatives as the model system. This is important because activation of paternal UBE3A through the suppression of UBE3A-ATS transcription is a promising therapeutic strategy for AS.