Evidence for translational regulation of the imprinted Snurf-Snrpn locus in mice.
In studies of genomic imprinting in the Prader-Willi/Angelman domain, an agouti coat color cassette was inserted into the downstream open reading frame (ORF) of the imprinted bicistronic Snurf-Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf-Snrpn, and produced a tan abdomen only when inherited paternally in otherwise-black mice. A screen for dominant epigenetic or genetic events was performed with ENU mutagenesis, using a strategy whereby variation in abdominal color was scored at weaning. One mouse with maternal origin of the fusion gene had a tan abdomen and had an imprinting defect resulting in loss of both maternal methylation and silencing of the fusion gene. One mouse with paternal origin of the fusion gene was completely yellow and was found to have an ATG-to-AAG mutation in the initiation codon of the upstream ORF encoding SNURF. Northern blotting, immunoblotting, and transfection studies indicated that the ATG-to-AAG mutation causes a 15-fold or more increase in translation of the downstream ORF in two fusion constructs, and it is likely that similar translational control affects the normal Snurf-Snrpn transcript as well.
Tsai
Ting-Fen
TF
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Chen
Ken-Shiung
KS
Weber
John S
JS
Justice
Monica J
MJ
Beaudet
Arthur L
AL
D054366:Agouti Signaling Protein; D000818:Animals; D018387:Codon, Initiator; D019175:DNA Methylation; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D020868:Gene Silencing; D017930:Genes, Reporter; D018392:Genomic Imprinting; D006200:Hair Color / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D054366:Agouti Signaling Protein; D018387:Codon, Initiator; D036341:Intercellular Signaling Peptides and Proteins; D009153:Mutagens; D009687:Nuclear Proteins; D011506:Proteins; C486713:SNURF protein, mouse; D005038:Ethylnitrosourea