title: Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is differentially regulated during neuronal differentiation of embryonic stem cells.
abstract: Here, we report on the discovery of a locus in the human genome, which evolved by gene duplication followed by an internal DNA inversion. This locus exhibits high sequence similarity to the gene for the inducible isoform of NOS protein (NOS2A) and is transcribed into a noncoding RNA containing a region of significant antisense homology with the NOS2A mRNA. We show that this antisense transcript (anti-NOS2A RNA) is expressed in different types of brain tumors, including meningiomas and glioblastomas. More importantly, we demonstrate that the expression profiles of the anti-NOS2A RNA and the NOS2A mRNA exhibit concurrent reciprocal changes in undifferentiated human embryonic stem cells (hESCs) and in hESCs induced to differentiate into neurogenic precursors such as neurospheres. As NOS2A has a role in neurogenesis, our results suggest that the anti-NOS2A RNA is involved in the regulation of neuronal differentiation of hESCs through the modulation of NOS2A gene expression.
authors.affiliation: Sussex Centre for Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom. s.korneev@sussex.ac.uk
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Korneev
authors.forename: Elena I
authors.initials: EI
authors.lastname: Korneeva
authors.forename: Marya A
authors.initials: MA
authors.lastname: Lagarkova
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kiselev
authors.forename: Giles
authors.initials: G
authors.lastname: Critchley
authors.forename: Michael
authors.initials: M
authors.lastname: O'Shea
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology; D020440:Gene Duplication; D015971:Gene Expression Regulation, Enzymologic; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016372:RNA, Antisense; D012333:RNA, Messenger; D022661:RNA, Untranslated; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II