SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome

Abstract

The imprinted domain on human chromosome 15 consists of two oppositely imprinted gene clusters, which are under the control of an imprinting center (IC). The paternally expressed SNURF-SNRPN gene hosts several snoRNA genes and overlaps the UBE3A gene, which is encoded on the opposite strand, expressed - at least in brain cells - from the maternal chromosome only, and affected in patients with Angelman syndrome (AS). In contrast to SNURF-SNRPN, imprinted expression of UBE3A is not regulated by a 5' differentially methylated region. Here we report that splice forms of the SNURF-SNRPN transcript overlapping UBE3A in an antisense orientation are present in brain but barely detectable in blood. In contrast, splice forms that do not overlap with UBE3A are of similar abundance in brain and blood. The tissue distribution of the splice forms parallels that of the snoRNAs encoded in the respective parts of the SNURF-SNRPN transcript. Using a quantitative PCR assay, we have found that the ratio of SNURF-SNRPN/UBE3A transcript levels is increased in blood cells of AS patients with an imprinting defect, but not in AS patients with a UBE3A mutation or an unknown defect. Our findings are compatible with the assumption that imprinted UBE3A expression is regulated through the SNURF-SNRPN sense- UBE3A antisense transcript.

Rapid Birth-and-Death Evolution of Imprinted snoRNAs in the Prader-Willi Syndrome Locus: Implications for Neural Development in Euarchontoglires

“…Typically, maternally expressed imprinted genes have effects on ‘higher’ cognitive systems, whereas paternal genes have effects on brain systems that fill ‘emotional’ or autonomic functions [72]. The 15q11–13 imprinted snoRNA cluster is paternally expressed in the adult brain [73], suggesting that these genes might be involved in emotional function. Several lines of evidence suggest that the evolution of the 15q11–13 snoRNA cluster has contributed to the fine control of emotion and the related social behaviors of individuals.…”

Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability

“…608636). 55 Whereas SNURF-SNRPN expression is also upregulated in these patients similarly to UPF3B patients, 55,56 little is known about its downstream consequences. It is possible that the upregulation of the SNURF-SNRPN gene contributes to the neurological features shared among patients with these disorders and those of the UPF3B patients, which include ID, seizures and autistic behaviors.…”

Synaptic Signaling and Aberrant RNA Splicing in Autism Spectrum Disorders

“…Most notably, affected genes include the SNURF–SNRPN complex and small nucleolar RNAs (snoRNAs) also encoded within SNRPN . The snoRNAs encoded within SNRPN regulate the expression of the anti-sense encoded UBE3A (Runte et al, 2004), which is particularly significant given the gene-dose dependent effect of this region on autistic phenotypes; i.e., maternal uniparental disomy results in greater incidence of ASD (Veltman et al, 2004). The protein encoded by UBE3A localizes to synapses in cerebellar Purkinje cells and pyramidal neurons of the hippocampus and cortex where it contributes to dendritic spine development (Dindot et al, 2008).…”