title: Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2.
abstract: The gene Mest (also known as Peg1) is regulated by genomic imprinting in the mouse and only the paternal allele is active for transcription. MEST is similarly imprinted in humans, where it is a candidate for the growth retardation Silver-Russell syndrome. The MEST protein belongs to an ancient family of hydrolases but its function is still unknown. It is highly conserved in vertebrates although imprinted expression is only observed in marsupials and eutherians, thus a recent evolutionary event. Here we describe the identification of new imprinted RNA products at the Mest locus, longer variants of the RNA, called MestXL, transcribed >10 kb into the downstream antisense gene Copg2. During development MestXL is produced exclusively in the developing central nervous system (CNS) by alternative polyadenylation. Copg2 is biallelically expressed in the embryo except in MestXL-expressing tissues, where we observed preferential expression from the maternal allele. To analyze the function of the MestXL transcripts in Copg2 regulation, we studied the effects of a targeted allele at Mest introducing a truncation in the mRNA. We show that both the formation of the MestXL isoforms and the allelic bias at Copg2 are lost in the CNS of mutants embryos. Our results propose a new mechanism to regulate allelic usage in the mammalian genome, via tissue-specific alternative polyadenylation and transcriptional interference in sense-antisense pairs at imprinted loci.
authors: Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, The University of British Columbia, Vancouver, Canada V6T 1Z3.
authors: Julia L
authors: JL
authors: MacIsaac
authors: Aaron B
authors: AB
authors: Bogutz
authors: A Sorana
authors: AS
authors: Morrissy
authors: Louis
authors: L
authors: Lefebvre
mesh_terms: D000483:Alleles; D000818:Animals; D020756:Coatomer Protein; D018392:Genomic Imprinting; D051379:Mice; D009154:Mutation; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D026723:Polyadenylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D020756:Coatomer Protein; C410034:Copg2 protein, mouse; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C103637:mesoderm specific transcript protein; D012313:RNA