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Related Concept Videos

Biological Causes of Schizophrenia01:29

Biological Causes of Schizophrenia

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Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
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Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders01:27

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Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
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Ribosome Profiling02:24

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Translation01:31

Translation

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Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
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Related Experiment Video

Updated: Jun 18, 2025

Polysome Profiling in Leishmania, Human Cells and Mouse Testis
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Analysis of single-cell transcriptome data from a mouse model implicates protein synthesis dysfunction in

Andrew E Weller1, Thomas N Ferraro2,3, Glenn A Doyle4

  • 1Molecular and Neural Basis of Psychiatric Disease Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 125 S. 31 St., Suite 2200, Philadelphia, PA, 19104, US. andrew.weller@pennmedicine.upenn.edu.

Genes & Genomics
|July 31, 2024
PubMed
Summary
This summary is machine-generated.

Genetic factors in schizophrenia were studied using Setd1a knockout mice. Gene expression analysis revealed altered protein synthesis and the EIF2 Signaling pathway, suggesting new therapeutic targets for schizophrenia.

Keywords:
BiomarkerGene Expression ProfilingMouse ModelRNA-SeqSchizophreniaSingle-Cell

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Schizophrenia is a debilitating mental disorder with significant genetic underpinnings.
  • The Setd1a gene has been identified as a potential risk factor in schizophrenia development.

Purpose of the Study:

  • To investigate gene expression alterations in heterozygous Setd1a knockout mice.
  • To gain insights into the molecular mechanisms of schizophrenia pathogenesis.

Main Methods:

  • Single-cell RNA sequencing (scRNAseq) was performed on the prefrontal cortex (PFC) and striatum of Setd1a+/- mice.
  • Cell type-specific differentially expressed genes (DEGs) and differential transcript usage (DTU) were identified.
  • Ingenuity Pathway Analysis (IPA) was used to determine affected biological pathways.

Main Results:

  • In the PFC, 273 unique DEGs and 675 gene peaks with DTU were found. In the striatum, 327 unique DEGs and 8 gene peaks with DTU were identified.
  • Analysis implicated pathways in protein synthesis, mitochondrial function, metabolism, and inflammation.
  • The 'EIF2 Signaling' pathway, crucial for protein synthesis regulation, was consistently identified across multiple analyses.

Conclusions:

  • Protein synthesis pathways, particularly 'EIF2 Signaling', are critically involved in schizophrenia.
  • These pathways represent potential targets for novel therapeutic strategies and biomarker development in schizophrenia research.