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Identification of long noncoding RNA s dysregulated in the midbrain of human cocaine abusers
Author(s) -
Ban Michael J.,
Savonen Candace L.,
Jia Hui,
Dachet Fabien,
Halter Steven D.,
Schmidt Carl J.,
Lipovich Leonard,
Kapatos Gregory
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13255
Subject(s) - rna , biology , long non coding rna , non coding rna , gene expression , gene , neuroscience , genetics
Abstract Maintenance of the drug‐addicted state is thought to involve changes in gene expression in different neuronal cell types and neural circuits. Midbrain dopamine ( DA ) neurons in particular mediate numerous responses to drugs of abuse. Long noncoding RNA s (lnc RNA s) regulate CNS gene expression through a variety of mechanisms, but next to nothing is known about their role in drug abuse. The proportion of lnc RNA s that are primate‐specific provides a strong rationale for their study in human drug abusers. In this study, we determined a profile of dysregulated putative lnc RNA s through the analysis of postmortem human midbrain specimens from chronic cocaine abusers and well‐matched control subjects ( n = 11 in each group) using a custom lnc RNA microarray. A dataset comprising 32 well‐annotated lnc RNA s with independent evidence of brain expression and robust differential expression in cocaine abusers is presented. For a subset of these lnc RNA s, differential expression was validated by quantitative real‐time PCR and cellular localization determined by in situ hybridization histochemistry. Examples of lnc RNA s exhibiting DA cell‐specific expression, different subcellular distributions, and covariance of expression with known cocaine‐regulated protein‐coding genes were identified. These findings implicate lnc RNA s in the cellular responses of human DA neurons to chronic cocaine abuse.Long noncoding RNAs (lncRNAs) regulate the expression of protein‐coding genes, but little is known about their potential role in drug abuse. In this study, we identified lncRNAs differentially expressed in human cocaine abusers' midbrains. One up‐regulated antisense lncRNA, tumor necrosis factor receptor‐associated factor 3‐interacting protein 2‐antisense 1 (TRAF3IP2‐AS1), was found predominantly in the nucleus of human dopamine (DA) neurons, whereas the related TRAF3IP2 protein‐coding transcript was distributed throughout these cells. The abundances of these transcripts were significantly correlated (left) suggesting that TRAF3IP2‐AS1 may regulate TRAF3IP2 gene expression, perhaps through local chromatin changes at this locus (right).