Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Loyal A. Goff, Abigail F. Groff, Martin Sauvageau, Zachary Trayes-Gibson, Diana B. Sanchez-Gomez, Michael Morse, Ryan D. Martin, Lara E. Elcavage, Stephen C. Liapis, Meryem Gonzalez-Celeiro, Olivia Plana, Eric Li, Chiara Gerhardinger, Giulio S. Tomassy, Paola Arlotta, John L. Rinn

Research output: Contribution to journalArticle

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring proteincoding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.

Original languageEnglish (US)
Pages (from-to)6855-6862
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number22
DOIs
StatePublished - Jun 2 2015

Keywords

  • Brain
  • Development
  • In vivo
  • Long noncoding rna
  • Mouse

ASJC Scopus subject areas

  • General

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    Goff, L. A., Groff, A. F., Sauvageau, M., Trayes-Gibson, Z., Sanchez-Gomez, D. B., Morse, M., Martin, R. D., Elcavage, L. E., Liapis, S. C., Gonzalez-Celeiro, M., Plana, O., Li, E., Gerhardinger, C., Tomassy, G. S., Arlotta, P., & Rinn, J. L. (2015). Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences of the United States of America, 112(22), 6855-6862. https://doi.org/10.1073/pnas.1411263112