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Neuronal-expressed microRNA-targeted pseudogenes compete with coding genes in the human brain

S Barbash1, A Simchovitz1, A S Buchman2

  • 1The Edmond &Lily Safra Center for Brain Sciences and the Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Translational Psychiatry
|August 9, 2017
PubMed

Insights

Non-coding pseudogenes with microRNA recognition elements (MREs) are involved in brain function and neuronal regulation. These pseudogenes (PSG+MRE) interact with microRNAs and coding transcripts, impacting brain development and potentially mental diseases.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs regulate brain function by binding to microRNA recognition elements (MREs) on target transcripts.
  • The competitive interactions between coding and non-coding transcripts sharing MREs within the microRNA pool are not well understood.

Purpose of the Study:

  • To investigate the role of non-coding pseudogenes carrying MREs (PSG+MRE) in the human brain.
  • To explore the functional involvement and regulatory interactions of PSG+MRE with microRNAs and coding transcripts.

Main Methods:

  • Comparative analysis of pseudogenes with and without MREs (PSG+MRE vs. PSG-MRE) in human temporal lobe neurons.
  • Detection of PSG+MRE in neuronal RNA-induced silencing complexes (RISC).
  • Cell culture experiments to assess co-regulation between PSG+MRE, MRE-sharing coding transcripts, and microRNAs.

Main Results:

  • Duplicated pseudogenes with MREs (PSG+MRE) are evolutionarily conserved and highly expressed in human temporal lobe neurons.
  • PSG+MRE are functional components of neuronal RISC.
  • Bidirectional co-regulation was observed between PSG+MRE and MRE-sharing coding transcripts (often not their parent genes) and targeted microRNAs.
  • Single-nucleotide polymorphisms in PSG+MRE are associated with schizophrenia, bipolar disorder, and autism.

Conclusions:

  • Duplicated pseudogenes with MREs play significant roles in human brain development and cognition.
  • Reciprocal co-regulation between PSG+MRE and MRE-sharing coding transcripts impacts neuronal function.
  • Pseudogene involvement in microRNA regulation may contribute to the etiology of mental diseases.

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