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Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...

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Related Experiment Video

Updated: Jul 9, 2026

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans
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Repeated Clozapine Administration Causes Extensive Changes to the Expression of Coding and Non-coding RNAs, Including

Rabha Mussa Younis1, Dalia Y Al Saeedy1, Mikhail G Dozmorov2

  • 1Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.

Molecular Neurobiology
|July 21, 2025
PubMed
Summary

Clozapine significantly alters gene expression and RNA splicing in the mouse brain, impacting microRNA-124 and schizophrenia risk genes. These findings offer potential biomarkers for clozapine treatment response.

Keywords:
Antipsychotic drugsBrainGene expressionNon-coding RNARNA sequencingSchizophrenia

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Area of Science:

  • Neuroscience
  • Genomics
  • Pharmacology

Background:

  • Clozapine is a highly effective antipsychotic for schizophrenia, yet its precise mechanisms remain unclear.
  • Understanding clozapine's molecular actions is crucial for improving schizophrenia treatment.

Purpose of the Study:

  • To investigate the effects of clozapine on gene transcription and RNA splicing in the mouse frontal cortex.
  • To integrate these findings with known schizophrenia risk genes to identify potential therapeutic targets.

Main Methods:

  • Deep RNA sequencing was employed to analyze differential mRNA and long noncoding RNA (lncRNA) expression and exon usage in mouse frontal cortex.
  • Mice were treated with clozapine (4 mg/kg/day for 21 days) followed by a 24-hour washout period.
  • Quantitative PCR was used to validate changes in specific microRNAs (miRNAs).

Main Results:

  • Clozapine significantly altered the expression of mRNAs and lncRNAs, particularly those involved in RNA processing and splicing.
  • The microRNA-124 host gene (Mir124a-1hg) was significantly upregulated, leading to increased levels of miR-124-3p.
  • Differential exon use analysis revealed that clozapine impacts mouse orthologs of 50 schizophrenia risk genes, enriched in neuronal development pathways.

Conclusions:

  • Clozapine profoundly affects cortical gene expression, influencing both coding and non-coding RNA abundance and splicing.
  • The observed effects on miR-124 and schizophrenia risk genes suggest potential mechanisms for clozapine's efficacy.
  • These findings may serve as preclinical markers for predicting clozapine response in schizophrenia patients.