Differential regulation of non-protein coding RNAs from Prader-Willi Syndrome locus

Sci Rep. 2014 Sep 23:4:6445. doi: 10.1038/srep06445.

Abstract

Prader-Willi Syndrome (PWS) is a neurogenetic disorder caused by the deletion of imprinted genes on the paternally inherited human chromosome 15q11-q13. This locus harbours a long non-protein-coding RNA (U-UBE3A-ATS) that contains six intron-encoded snoRNAs, including the SNORD116 and SNORD115 repetitive clusters. The 3'-region of U-UBE3A-ATS is transcribed in the cis-antisense direction to the ubiquitin-protein ligase E3A (UBE3A) gene. Deletion of the SNORD116 region causes key characteristics of PWS. There are few indications that SNORD115 might regulate serotonin receptor (5HT2C) pre-mRNA processing. Here we performed quantitative real-time expression analyses of RNAs from the PWS locus across 20 human tissues and combined it with deep-sequencing data derived from Cap Analysis of Gene Expression (CAGE-seq) libraries. We found that the expression profiles of SNORD64, SNORD107, SNORD108 and SNORD116 are similar across analyzed tissues and correlate well with SNORD116 embedded U-UBE3A-ATS exons (IPW116). Notable differences in expressions between the aforementioned RNAs and SNORD115 together with the host IPW115 and UBE3A cis-antisense exons were observed. CAGE-seq analysis revealed the presence of potential transcriptional start sites originated from the U-UBE3A-ATS spanning region. Our findings indicate novel aspects for the expression regulation in the PWS locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons / genetics*
  • Gene Expression Regulation*
  • Genomic Imprinting
  • Humans
  • Prader-Willi Syndrome / genetics*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • RNA, Small Nucleolar / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Small Nucleolar
  • UBE3A protein, human
  • Ubiquitin-Protein Ligases