# Regulation of UBE3A Imprinted Expression

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $416,575

## Abstract

SUMMARY
Imprinted expression of UBE3A is neuron-specific and occurs because the paternally-inherited allele is
silenced. A long non-coding antisense transcript, UBE3A-ATS, is expressed in a neuron-specific manner and
mediates UBE3A imprinting by an unknown mechanism. The overall goal of this proposal is to understand
the processes underlying the regulation of neuron-specific expression of UBE3A-ATS and repression
of paternal UBE3A in human neurons. We propose to investigate three different aspects regulating UBE3A
imprinted expression: 1) the regulation of coding versus non-coding SNRPN RNAs in human neurons; 2) the
tissue-specific regulation of UBE3A-ATS, the distal portion of the SNRPN ncRNA; and 3) the mechanism by
which UBE3A-ATS leads to the repression of paternal UBE3A. We will use patient-specific induced pluripotent
stem cells (iPSCs) derived from Angelman syndrome (AS) patients and their neuronal derivatives for these
studies. We will dissect the functional elements of the cis-acting boundary element restricting UBE3A-ATS
expression to neurons and determine the developmental timing of their removal. We will determine how
SNRPN coding versus non-coding RNA is produced and manipulate expression levels of UBE3A-ATS and
UBE3A to determine their effect on UBE3A imprinting. Finally, we will test the hypothesis that UBE3A-ATS
silences paternal UBE3A via a transcriptional interference mechanism. A thorough understanding of the
mechanisms underlying UBE3A imprinted expression may reveal novel gene regulatory mechanisms
applicable elsewhere in the genome, and may identify novel therapeutic targets for treating AS.

## Key facts

- **NIH application ID:** 10255508
- **Project number:** 5R01HD094953-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Brenton R. Graveley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,575
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10255508

## Citation

> US National Institutes of Health, RePORTER application 10255508, Regulation of UBE3A Imprinted Expression (5R01HD094953-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10255508. Licensed CC0.

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