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. 2008 Jan 15;105(2):716-21.
doi: 10.1073/pnas.0706729105. Epub 2008 Jan 9.

Specific expression of long noncoding RNAs in the mouse brain

Tim R Mercer  1 , Marcel E Dinger, Susan M Sunkin, Mark F Mehler, John S Mattick
Affiliations

Specific expression of long noncoding RNAs in the mouse brain

Tim R Mercer et al. Proc Natl Acad Sci U S A. .

Abstract

A major proportion of the mammalian transcriptome comprises long RNAs that have little or no protein-coding capacity (ncRNAs). Only a handful of such transcripts have been examined in detail, and it is unknown whether this class of transcript is generally functional or merely artifact. Using in situ hybridization data from the Allen Brain Atlas, we identified 849 ncRNAs (of 1,328 examined) that are expressed in the adult mouse brain and found that the majority were associated with specific neuroanatomical regions, cell types, or subcellular compartments. Examination of their genomic context revealed that the ncRNAs were expressed from diverse places including intergenic, intronic, and imprinted loci and that many overlap with, or are transcribed antisense to, protein-coding genes of neurological importance. Comparisons between the expression profiles of ncRNAs and their associated protein-coding genes revealed complex relationships that, in combination with the specific expression profiles exhibited at both regional and subcellular levels, are inconsistent with the notion that they are transcriptional noise or artifacts of chromatin remodeling. Our results show that the majority of ncRNAs are expressed in the brain and provide strong evidence that the majority of processed transcripts with no protein-coding capacity function intrinsically as RNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Regionally enriched expression of ncRNAs in the hippocampus, cerebral cortex, and cerebellum. ISH images of ncRNA expression (accession nos. indicated) in sagittal plane accompanied by false-color heat map below. (a) No probe control in hippocampus, with the functionally distinct CA1, CA2, CA3, and dentate gyrus (DG) subfields indicated. (b–d) Enriched ncRNA expression in DG (b) and CA1–CA3 (c) and DG and CA1 in combination (d). (e) No probe control with labeled cortical layer boundaries. (f–h) Enriched ncRNA expression that correlates with specific cortical laminae. (i) No probe control in cerebellum, with the molecular (MO), Purkinje (PU), and granular (GR) layers indicated on detailed Inset. (j–l) Enriched ncRNA expression associated with cerebellar subregions. ncRNA AK082312 (l) is transcribed opposite Cbln1, a gene crucial in maintaining the synapse integrity and plasticity in Purkinje cells (62). Further examples are illustrated in SI Figs. 11–14.
Fig. 2.
Fig. 2.
Expression of ncRNAs associated with protein-coding genes. (a–c) cis-antisense. (a) No probe control showing cerebellum in sagittal plane. (b) P-rex1 is specifically expressed in the Purkinje cell layer in the cerebellum. (c) In contrast, an ncRNA that is transcribed antisense to the P-rex1 3′ UTR is expressed throughout the granular layer and in a restricted subcellular manner within Purkinje cells. (d–f) Bidirectional pairs. (d) No probe control of cerebral cortex in coronal plane (CX). Satb2 is expressed in the cerebral cortex (e) similar to an ncRNA transcribed opposite the Satb2 gene (f). (g–i) Intronic. (g) No probe control showing labeled hippocampus in sagittal plane. Odz3 is expressed in a gradient in the CA1 hippocampal subfield (h) in contrast to an ncRNA located in a Odz3 intron that is strongly expressed throughout the hippocampus proper (i). Further examples are illustrated in SI Fig. 15.
Fig. 3.
Fig. 3.
Expression of Coup-TfII and imprinted antisense ncRNA. (a) No probe control in sagittal plane showing detail of thalamus (Inset i) and ventral hippocampus (Inset ii). (b) Imprinted antisense ncRNA AK045070 is expressed in the cortical amygdala area (red arrow), reticular nucleus of the thalamus (Inset i), and the ventral hippocampus (Inset ii). (c) Coup-TfII is similarly expressed in the reticular nucleus of the thalamus (Inset i) and in the piriform cortex with additional expression in the granular and Purkinje cell layers of the cerebellum, the ventral (Inset ii) and dorsal hippocampus.
Fig. 4.
Fig. 4.
Subcellular localization of ncRNAs. (a) No probe control showing Purkinje cell layer (PU) in cerebellum in sagittal plane. (b–e) ncRNAs exhibiting a range of subcellular expression profiles within Purkinje cells: (b) expressed throughout the soma; (c) expressed throughout the nucleus (ncRNAs known to be exclusively retained in the nucleus were used as indicators for nuclear staining; see SI Fig. 18); (d) expressed as twin nuclear foci; (e) expressed as multiple foci; and (f) expressed in proximal neurite extensions in the hippocampus. Further examples are illustrated in SI Fig. 18.
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