Developmental changes in the transcriptome of human cerebral cortex tissue: long noncoding RNA transcripts.

The human neocortex is characterized by protracted developmental intervals of synaptogenesis and myelination, which allow for an extended period of learning. The molecular basis of these and other postnatal developmental changes in the human cerebral cortex remain incompletely understood. Recently, a new large class of mammalian genes, encoding nonmessenger, long nonprotein-coding ribonucleic acid (lncRNA) molecules has been discovered. Although their function remains uncertain, numerous lncRNAs have primate-specific sequences and/or show evidence of rapid, lineage-specific evolution, making them potentially relevant to the evolution of unique human neural properties. To examine the hypothesis that lncRNA expression varies with age, potentially paralleling known developmental trends in synaptogenesis, myelination, and energetics, we quantified levels of nearly 6000 lncRNAs in 36 surgically resected human neocortical samples (primarily derived from temporal cortex) spanning infancy to adulthood. Our analysis identified 8 lncRNA genes with distinct developmental expression patterns. These lncRNA genes contained anthropoid-specific exons, as well as splice sites and polyadenylation signals that resided in primate-specific sequences. To our knowledge, our study is the first to describe developmental expression profiles of lncRNA in surgically resected in vivo human brain tissue. Future analysis of the functional relevance of these transcripts to neural development and energy metabolism is warranted.

[1]  L. Lipovich,et al.  Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks , 2012, Genetics.

[2]  J. Loeb,et al.  Layer-Specific CREB Target Gene Induction in Human Neocortical Epilepsy , 2012, Journal of Neuroscience.

[3]  Claes Wahlestedt,et al.  Involvement of long noncoding RNAs in diseases affecting the central nervous system , 2012, RNA biology.

[4]  P. Hof,et al.  Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults , 2012, PloS one.

[5]  M. Kyba,et al.  The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r , 2012, Nature Cell Biology.

[6]  J. Kleinman,et al.  Spatiotemporal transcriptome of the human brain , 2011, Nature.

[7]  Jeannie T. Lee,et al.  A Boundary Element Between Tsix and Xist Binds the Chromatin Insulator Ctcf and Contributes to Initiation of X-Chromosome Inactivation , 2011, Genetics.

[8]  J. Rinn,et al.  lincRNAs act in the circuitry controlling pluripotency and differentiation , 2011, Nature.

[9]  C. Lebel,et al.  Longitudinal Development of Human Brain Wiring Continues from Childhood into Adulthood , 2011, The Journal of Neuroscience.

[10]  G. Šimić,et al.  Extraordinary neoteny of synaptic spines in the human prefrontal cortex , 2011, Proceedings of the National Academy of Sciences.

[11]  T. Derrien,et al.  De longs ARN non codants activateurs de la transcription des gènes , 2011 .

[12]  S. Pääbo,et al.  Rapid metabolic evolution in human prefrontal cortex , 2011, Proceedings of the National Academy of Sciences.

[13]  Leonard Lipovich,et al.  Mining Affymetrix microarray data for long non‐coding RNAs: altered expression in the nucleus accumbens of heroin abusers , 2011, Journal of neurochemistry.

[14]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[15]  Michael Q. Zhang,et al.  A long nuclear‐retained non‐coding RNA regulates synaptogenesis by modulating gene expression , 2010, EMBO Journal.

[16]  Jonathan D. Power,et al.  The Development of Human Functional Brain Networks , 2010, Neuron.

[17]  Leonard Lipovich,et al.  MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. , 2010, Biochimica et biophysica acta.

[18]  Leonard Lipovich,et al.  Genome-wide computational identification and manual annotation of human long noncoding RNA genes. , 2010, RNA.

[19]  G. Chrousos,et al.  Noncoding RNA Gas5 Is a Growth Arrest– and Starvation-Associated Repressor of the Glucocorticoid Receptor , 2010, Science Signaling.

[20]  P. Robson,et al.  Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. , 2010, RNA.

[21]  J. Disterhoft,et al.  Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. , 2009, Nature neuroscience.

[22]  L. Lipovich,et al.  Global discovery of primate-specific genes in the human genome , 2009, Proceedings of the National Academy of Sciences.

[23]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[24]  D. Spector,et al.  Long noncoding RNAs: functional surprises from the RNA world. , 2009, Genes & development.

[25]  S. Pääbo,et al.  Transcriptome analysis of male–female differences in prefrontal cortical development , 2009, Molecular Psychiatry.

[26]  Vetle I. Torvik,et al.  Natural antisense transcripts are co-expressed with sense mRNAs in synaptoneurosomes of adult mouse forebrain , 2008, Neuroscience Research.

[27]  D. Johnston,et al.  Identification of Testis‐Specific Male Contraceptive Targets , 2007, Annals of the New York Academy of Sciences.

[28]  Piero Carninci,et al.  Noncoding RNA transcription beyond annotated genes. , 2007, Current opinion in genetics & development.

[29]  Vladimir A. Kuznetsov,et al.  Quality Assessment of the Affymetrix U133A&B Probesets by Target Sequence Mapping and Expression Data Analysis , 2007, Silico Biol..

[30]  Yusuke Nakamura,et al.  Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction , 2006, Journal of Human Genetics.

[31]  M. Bannon,et al.  Distinctive Profiles of Gene Expression in the Human Nucleus Accumbens Associated with Cocaine and Heroin Abuse , 2006, Neuropsychopharmacology.

[32]  E. Blackburn,et al.  Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging , 2006, Nature Medicine.

[33]  D. Haussler,et al.  An RNA gene expressed during cortical development evolved rapidly in humans , 2006, Nature.

[34]  J. Harrow,et al.  GENCODE: producing a reference annotation for ENCODE , 2006, Genome Biology.

[35]  E. Birney,et al.  EGASP: the human ENCODE Genome Annotation Assessment Project , 2006, Genome Biology.

[36]  Sin Lam Tan,et al.  Complex Loci in Human and Mouse Genomes , 2006, PLoS genetics.

[37]  S. Batalov,et al.  A Strategy for Probing the Function of Noncoding RNAs Finds a Repressor of NFAT , 2005, Science.

[38]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[39]  M. Batzer,et al.  Alu repeats and human genomic diversity , 2002, Nature Reviews Genetics.

[40]  P. Huttenlocher,et al.  Regional differences in synaptogenesis in human cerebral cortex , 1997, The Journal of comparative neurology.

[41]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[42]  J. Mazziotta,et al.  Positron emission tomography study of human brain functional development , 1987, Annals of neurology.