Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing

Science. 2012 Dec 14;338(6113):1469-72. doi: 10.1126/science.1228110.

Abstract

Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with RNA polymerase II recruitment in the absence of repressive chromatin. Such a repressor function for lncRNA transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of lncRNA transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cells, Cultured
  • Gene Silencing*
  • Genomic Imprinting*
  • Mice
  • Multigene Family
  • Promoter Regions, Genetic
  • RNA Polymerase II / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptor, IGF Type 2 / genetics*
  • Transcription, Genetic*

Substances

  • Air non-coding RNA, mouse
  • RNA, Long Noncoding
  • Receptor, IGF Type 2
  • RNA Polymerase II

Associated data

  • GEO/GSE41444