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Identification and analysis of intermediate size noncoding RNAs in the human fetal brain.

ABSTRACT: The involvement of noncoding RNAs (ncRNAs) in the development of the human brain remains largely unknown. Applying a cloning strategy for detection of intermediate size (50-500 nt) ncRNAs (is-ncRNAs) we have identified 82 novel transcripts in human fetal brain tissue. Most of the novel is-ncRNAs are not well conserved in vertebrates, and several transcripts were only found in primates. Northern blot and microarray analysis indicated considerable variation in expression across human fetal brain development stages and fetal tissues for both novel and known is-ncRNAs. Expression of several of the novel is-ncRNAs was conspicuously absent in one or two brain cancer cell lines, and transient overexpression of some transcripts in cancer cells significantly inhibited cell proliferation. Overall, our results suggest that is-ncRNAs play important roles in the development and tumorigenesis of human brain.

SUBMITTER: Yan D

PROVIDER: S-EPMC3138756 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Identification and analysis of intermediate size noncoding RNAs in the human fetal brain.

Yan Dongsheng D He Dandan D He Shunmin S Chen Xiaoyan X Fan Zhen Z Chen Runsheng R

PloS one 20110718 7

The involvement of noncoding RNAs (ncRNAs) in the development of the human brain remains largely unknown. Applying a cloning strategy for detection of intermediate size (50-500 nt) ncRNAs (is-ncRNAs) we have identified 82 novel transcripts in human fetal brain tissue. Most of the novel is-ncRNAs are not well conserved in vertebrates, and several transcripts were only found in primates. Northern blot and microarray analysis indicated considerable variation in expression across human fetal brain d ...[more]

PMID: 21789175

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Project description: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 RNAs (lncRNAs) regulate CNS gene expression through a variety of mechanisms, but next to nothing is known about their role in drug abuse. The proportion of lncRNAs 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 lncRNAs 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 lncRNA microarray. A dataset comprising 32 well-annotated lncRNAs with independent evidence of brain expression and robust differential expression in cocaine abusers is presented. For a subset of these lncRNAs, differential expression was validated by quantitative real-time PCR and cellular localization determined by in situ hybridization histochemistry. Examples of lncRNAs exhibiting DA cell-specific expression, different subcellular distributions, and covariance of expression with known cocaine-regulated protein-coding genes were identified. These findings implicate lncRNAs 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).

Dataset Information

Identification and analysis of intermediate size noncoding RNAs in the human fetal brain.

Publications

Identification and analysis of intermediate size noncoding RNAs in the human fetal brain.

Similar Datasets

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