A genome-wide enhancer/suppressor screen for Dube3a interacting genes in Drosophila melanogaster

• Published in: Scientific reports Vol. 9; no. 1; p. 2382
• Main Authors: Hope, Kevin A., McGinn, Addison, Reiter, Lawrence T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-02-2019; Nature Publishing Group
• Subjects: 14/19; 14/35; 45; 631/208/366/1373; 631/378/2583; 64/24; Autism; Drosophila melanogaster; Genetics; Genomes; Humanities and Social Sciences; Insects; multidisciplinary; Phenotypes; Science; Science (multidisciplinary); Transcription activation; Ubiquitin; Ubiquitin-protein ligase; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-38663-y

The genetics underlying autism spectrum disorder (ASD) are complex. Approximately 3–5% of ASD cases arise from maternally inherited duplications of 15q11.2-q13.1, termed Duplication 15q syndrome (Dup15q). 15q11.2-q13.1 includes the gene
UBE3A
which is believed to underlie ASD observed in Dup15q syndrome. UBE3A is an E3 ubiquitin ligase that targets proteins for degradation and trafficking, so finding UBE3A substrates and interacting partners is critical to understanding Dup15q ASD. In this study, we take an unbiased genetics approach to identify genes that genetically interact with
Dube3a
, the
Drosophila melanogaster
homolog of
UBE3A
. We conducted an enhancer/suppressor screen using a rough eye phenotype produced by
Dube3a
overexpression with
GMR-
GAL4. Using the DrosDel deficiency kit, we identified 3 out of 346 deficiency lines that enhanced rough eyes when crossed to two separate
Dube3a
overexpression lines, and subsequently identified
IA2
,
GABA-B-R3
, and
lola
as single genes responsible for rough eye enhancement. Using the FlyLight GAL4 lines to express
uas-Dube3a
 + 
uas-GFP
in the endogenous
lola
pattern, we observed an increase in the GFP signal compared to
uas-GFP
alone, suggesting a transcriptional co-activation effect of
Dube3a
on the
lola
promoter region. These findings extend the role of
Dube3a/UBE3A
as a transcriptional co-activator, and reveal new
Dube3a
interacting genes.