Dynamic developmental regulation of the large non-coding RNA associated with the mouse 7C imprinted chromosomal region.
The mouse ortholog of the Prader-Willi/Angelman syndrome imprinted domain contains several paternal-specific transcripts and the maternally expressed gene encoding ubiquitin protein ligase E3A (Ube3a). A Large paternal Non-Coding RNA, encompassing Snurf-Snrpn exons and the Ube3a Antisense Transcript (Ube3a-ATS), has been recently characterized and named here LNCAT. Potential roles of LNCAT in imprinting, gene regulation, and disease are likely but have not been investigated. In order to establish the function(s) of LNCAT, we first determined its in vivo spatio-temporal expression pattern at the cellular level during development and in different adult brain tissues. We show here that LNCAT is developmentally regulated, with transcript variants being specifically expressed through neuronal differentiation in postmitotic neurons. We demonstrate that the LNCAT and Snurf-Snrpn transcripts are independent although they share common exons. We show an absence of expression of LNCAT through gametogenesis and in early embryo excluding a role of LNCAT in the imprint establishment. We also report a range of observations that challenges the widely accepted model of imprinted gene silencing of Ube3a. Although these last data do not completely exclude that the LNCAT variants including "Ube3a-ATS"exons could repress the paternal allele of Ube3a, they do allow us to propose an alternative and consistent model.
Le Meur
Elodie
E
NMDA/IBDM, Campus de Luminy Case 907 13288 Marseille Cedex 09, France.
Watrin
Françoise
F
Landers
Miguel
M
Sturny
Rachel
R
Lalande
Marc
M
Muscatelli
Françoise
F
D000818:Animals; D001324:Autoantigens; D033481:Chromosomes, Mammalian; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000235:genetics; D011218:Prader-Willi Syndrome; D022661:RNA, Untranslated / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055517:snRNP Core Proteins
D001324:Autoantigens; D009687:Nuclear Proteins; D022661:RNA, Untranslated; D017411:Ribonucleoproteins, Small Nuclear; C486713:SNURF protein, mouse; D055517:snRNP Core Proteins; C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases