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Comprehensive Analysis of Transcription Dynamics from Brain Samples Following Behavioral Experience
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Published on: August 26, 2014

Activity-dependent human brain coding/noncoding gene regulatory networks.

Leonard Lipovich1, Fabien Dachet, Juan Cai

  • 1Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48202, USA

Genetics
|September 11, 2012
PubMed
Summary
This summary is machine-generated.

Long noncoding RNAs (lncRNAs) regulate brain plasticity. A primate-specific lncRNA, BDNFOS, inversely controls brain-derived neurotrophic factor (BDNF) expression, impacting neuronal activity and memory.

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Most human genome transcription yields protein-coding RNA, but a significant portion produces noncoding RNAs with regulatory roles.
  • The brain-derived neurotrophic factor (BDNF) gene, crucial for neuronal activity, is regulated by a primate-specific long noncoding RNA (lncRNA) named BDNFOS.
  • lncRNAs are increasingly recognized for their roles in complex biological processes, including brain function.

Purpose of the Study:

  • To investigate the role of lncRNAs in activity-dependent human brain transcription.
  • To identify lncRNAs that are co-expressed or adjacent to activity-dependent protein-coding genes.
  • To elucidate the regulatory relationship between BDNFOS and BDNF in neuronal activity.

Main Methods:

  • Genome-wide analysis of human neocortex tissue using a custom lncRNA microarray.
  • Analysis of activity-dependent coding and noncoding transcription.
  • In vitro studies using SY5Y cells with repeated depolarization to mimic neuronal activity.
  • RNA interference (RNAi) to knockdown BDNFOS expression.

Main Results:

  • Identified 1288 differentially expressed lncRNAs, with 26 co-expressed with activity-dependent genes and 8 adjacent to or overlapping with such genes.
  • Demonstrated reciprocal transcription patterns of BDNF and BDNFOS in active human neocortex.
  • Showed that chronic neuronal depolarization in SY5Y cells leads to sustained CREB activation and inverse BDNF-BDNFOS co-expression.
  • Found that BDNFOS knockdown increases BDNF expression, indicating BDNFOS directly downregulates BDNF.

Conclusions:

  • lncRNAs, including primate-specific ones like BDNFOS, play significant regulatory roles in activity-dependent human brain plasticity.
  • BDNFOS acts as a direct negative regulator of BDNF expression.
  • Chronic neuronal activity influences the lncRNA-mRNA transcriptome, suggesting diverse lncRNA regulatory mechanisms in the brain.