The molecular structure and imprinting status of the IPW (imprinted gene in the Prader‐Willi syndrome region) gene in cattle

Abstract

IPW (imprinted gene in the Prader-Willi syndrome region), a long non-coding RNA, is a paternally expressed gene in the PWS/AS imprinted domain on human chromosome 15 and mouse chromosome 7. Disruption of the PWS/AS region is associated with three neurogenic disorders in humans. In this study, we identified the bovine homolog of the IPW gene; multiple transcripts obtained by RT-PCR and RACE showed a complex and tissuespecific expression pattern of IPW in the brain, heart, kidney, liver, lung, spleen and skeletal muscle. An informative single nucleotide polymorphism (rs133341090) in the long exon H was identified by sequencing the genomic DNA, and mono-allelic expression of IPW was confirmed by sequencing the cDNAs of heterozygous individuals, indicating that IPW may be imprinted in cattle. The protein-coding potential of IPW transcripts was assessed using CODING POTENTIAL CALCULATOR (CPC) software, which showed a negative score. In addition, sequencing analysis also indicated multiple small open reading frames in the bovine IPW transcript, but none of the ATGs was consistent with Kozak consensus. Taken together, the IPW transcripts are most likely long non-coding RNAs.

Imprinted gene in the Prader-Willi syndrome region (IPW) is differentially expressed in the brains of patients with psychotic disorders.

“…In mice, IPW is expressed in the brain in adults as well as during development (9,10). In cattle, IPW is expressed in the brain, heart, kidney, liver, lung, spleen, and skeletal muscle (5).…”

“…IPW likely encodes a non-coding RNA (4,5); none of the IPW transcripts produced in cattle contain Kozak consensus sequences (5). The IPW may actually be one extended transcript representing the host gene for a series of tandemly repeated, imprinted snoRNAs (11).…”

Proteins and proteases of Prader–Willi syndrome: a comprehensive review and perspectives

“…Among these proteins, MAGEL-2 and NECDIN have been strongly implicated in some of the pathophysiologies and abnormalities observed with PWS individuals. The rest of the proteins that also include IPW (ImPrinted gene in the Prader-Willi syndrome region) [51], PWRN1 (Prader-Willi Region Non-protein coding RNA-1) [52], SNORD-116 (Small NucleOlar RNA, C/D box 116) (53) have been either proposed or inadequately linked to some conditions like neurological abnormalities of PWS based on limited clinical and/or model animal studies. In particular, microdeletion in SNORD-116 may be linked to PWS conditions of some individuals but not for others [53].…”