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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1411263112

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

Publication TypeJournal Article
Year of Publication2015
AuthorsGoff, LA, Groff, AF, Sauvageau, M, Trayes-Gibson, Z, Sanchez-Gomez, DB, Morse, M, Martin, RD, Elcavage, LE, Liapis, SC, Gonzalez-Celeiro, M, Plana, O, Li, E, Gerhardinger, C, Tomassy, GS, Arlotta, P, Rinn, JL
JournalProc Natl Acad Sci U S A
Date Published2015 Jun 02
KeywordsAnimals, Base Sequence, beta-Galactosidase, Brain, Gene Expression Profiling, Gene Expression Regulation, Immunohistochemistry, Mice, Mice, Knockout, Microscopy, Confocal, Molecular Sequence Data, RNA, Long Noncoding, Sequence Analysis, DNA

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 lncRNAnull 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.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID26034286
PubMed Central IDPMC4460505
Grant ListR01MH102416-0 / MH / NIMH NIH HHS / United States
R01 NS062849 / NS / NINDS NIH HHS / United States
R01 MH101268 / MH / NIMH NIH HHS / United States
R01 MH102416 / MH / NIMH NIH HHS / United States
R01MH101268 / MH / NIMH NIH HHS / United States
R01NS062849 / NS / NINDS NIH HHS / United States