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CRISPR and crRNAs02:53

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Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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Related Experiment Video

Updated: Oct 23, 2025

Determining the Role of Maternally-Expressed Genes in Early Development with Maternal Crispants
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Systematic functional interrogation of human pseudogenes using CRISPRi.

Ming Sun1,2, Yunfei Wang1,3, Caishang Zheng1

  • 1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Genome Biology
|August 24, 2021
PubMed
Summary
This summary is machine-generated.

Human pseudogenes, once thought nonfunctional, are revealed to impact cancer cell fitness. A new study identifies specific pseudogenes, like MGAT4EP, that play roles in cancer development, highlighting their importance in human diseases.

Keywords:
CRISPR interferenceCancerFOXA1FOXM1GTExLuminal A breast cancerNucleusPseudogeneTCGATranscriptional regulationUnitary pseudogene

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Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Human genome contains over 14,000 pseudogenes, considered evolutionary relics.
  • Emerging evidence suggests potential functions for some pseudogenes, but large-scale characterization is lacking.
  • Technical challenges, including sequence similarity and poor annotation, hinder pseudogene functional studies.

Purpose of the Study:

  • To overcome technical obstacles in pseudogene research.
  • To perform the first genome-wide functional screen of human pseudogenes.
  • To investigate the role of pseudogenes in breast cancer cell fitness.

Main Methods:

  • Developed an integrated computational pipeline for CRISPR interference (CRISPRi) sgRNA library design.
  • Targeted pseudogene promoter-proximal regions for genome-wide screening.
  • Utilized CRISPRi screening in luminal A breast cancer cells.

Main Results:

  • Identified approximately 70 pseudogenes affecting breast cancer cell fitness.
  • Discovered MGAT4EP, a nuclear-localized pseudogene interacting with FOXA1 in breast cancer.
  • MGAT4EP enhances FOXA1 binding, upregulating oncogenic FOXM1 expression.
  • Found dysregulated expression of unitary pseudogenes associated with patient survival across various cancers.

Conclusions:

  • This is the first large-scale study characterizing pseudogene function.
  • Highlights the importance of nuclear functions of unitary pseudogenes in human diseases.
  • Suggests underappreciated roles for pseudogenes in disease pathogenesis.
  • Provides functional genomic resources to advance pseudogene research.