High expression of long intervening non-coding RNA OLMALINC in the human cortical white matter is associated with regulation of oligodendrocyte maturation

Mol Brain. 2015 Jan 10:8:2. doi: 10.1186/s13041-014-0091-9.

Abstract

Background: Long intervening non-coding RNAs (lincRNAs) are a recently discovered subclass of non-coding RNAs. LincRNAs are expressed across the mammalian genome and contribute to the pervasive transcription phenomenon. They display a tissue-specific and species-specific mode of expression and are present abundantly in the brain.

Results: Here, we report the expression patterns of oligodendrocyte maturation-associated long intervening non-coding RNA (OLMALINC), which is highly expressed in the white matter (WM) of the human frontal cortex compared to the grey matter (GM) and peripheral tissues. Moreover, we identified a novel isoform of OLMALINC that was also up-regulated in the WM. RNA-interference (RNAi) knockdown of OLMALINC in oligodendrocytes, which are the major cell type in the WM, caused significant changes in the expression of genes regulating cytostructure, cell activation and membrane signaling. Gene ontology enrichment analysis revealed that over 10% of the top 25 up- and down-regulated genes were involved in oligodendrocyte maturation. RNAi experiments in neuronal cells resulted in the perturbation of genes controlling cell proliferation. Furthermore, we identified a novel cis-natural antisense non-coding RNA, which we named OLMALINC-AS, which maps to the first exon of the dominant isoform of OLMALINC.

Conclusions: Our study has demonstrated for the first time that a primate-specific lincRNA regulates the expression of genes critical to human oligodendrocyte maturation, which in turn might be regulated by an antisense counterpart.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alternative Splicing / genetics
  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Cerebral Cortex / metabolism*
  • Exons / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • Gene Ontology
  • Genetic Loci
  • Genome, Human
  • Gray Matter / metabolism
  • Humans
  • Mammals / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism*
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Sequence Analysis, RNA
  • Signal Transduction / genetics
  • White Matter / metabolism*

Substances

  • RNA, Antisense
  • RNA, Long Noncoding