Related Experiment Video

Updated: May 1, 2026

Large-scale Gene Knockdown in C. elegans Using dsRNA Feeding Libraries to Generate Robust Loss-of-function Phenotypes
18:38

Large-scale Gene Knockdown in C. elegans Using dsRNA Feeding Libraries to Generate Robust Loss-of-function Phenotypes

Published on: September 25, 2013

11.5K

Mutation of a Nopp140 gene dao-5 alters rDNA transcription and increases germ cell apoptosis in C. elegans

C-C Lee1, Y-T Tsai2, C-W Kao3

  • 1Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.

Cell Death & Disease
|April 12, 2014
PubMed

Insights

A C. elegans dao-5 mutant models Nopp140-associated ribosomopathy, showing impaired ribosome biogenesis and germline defects. This model offers insights into human diseases like Treacher Collins syndrome.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Ribosomopathies are human diseases caused by impaired ribosome biogenesis.
  • Treacher Collins syndrome (TCS) is a ribosomopathy linked to mutations in the TCOF1 gene, which has a homolog in C. elegans called nopp140.
  • DAO-5 (dauer and aged animal overexpression gene 5) in C. elegans is a nopp140 family member involved in early embryonic nucleogenesis.

Purpose of the Study:

  • To establish a C. elegans model for studying Nopp140-associated ribosomopathy.
  • To investigate the cellular and molecular mechanisms underlying DAO-5 loss-of-function phenotypes.

Main Methods:

  • Generated a null dao-5 mutant (ok542) in C. elegans.
  • Phenotypic analysis including gonadogenesis delay and germline apoptosis.
  • Assessed rDNA transcription using run-on assays and chromatin immunoprecipitation (ChIP) for RNA Pol I occupancy.
  • Investigated histone modifications (H4Ac, H3K9me2) at the rDNA promoter via ChIP.
  • Analyzed CEP-1 (C. elegans p53 homolog) activity and its downstream effectors (EGL-1, CED-13).

Main Results:

  • The dao-5(ok542) mutant exhibited semi-infertility, delayed gonadogenesis, and increased germline apoptosis.
  • DAO-5 loss led to inefficient rDNA transcription, evidenced by reduced RNA Pol I occupancy at the rDNA promoter.
  • Altered histone modifications (H4Ac, H3K9me2) were observed around the rDNA promoter in dao-5 mutants.
  • CEP-1 activity was activated in dao-5 mutants, with upregulated expression of its targets EGL-1 and CED-13.

Conclusions:

  • The C. elegans dao-5 mutant serves as a valuable model for Nopp140-associated ribosomopathies.
  • DAO-5 is crucial for efficient rDNA transcription and maintaining genomic stability, likely through epigenetic regulation.
  • The findings provide cellular and molecular insights into the pathogenesis of human ribosomopathies like TCS.

More Related Videos

Application of a C. elegans Dopamine Neuron Degeneration Assay for the Validation of Potential Parkinson's Disease Genes08:42

Application of a C. elegans Dopamine Neuron Degeneration Assay for the Validation of Potential Parkinson's Disease Genes

Published on: July 18, 2008

15.2K
Application of RNAi and Heat-shock-induced Transcription Factor Expression to Reprogram Germ Cells to Neurons in C. elegans07:53

Application of RNAi and Heat-shock-induced Transcription Factor Expression to Reprogram Germ Cells to Neurons in C. elegans

Published on: January 1, 2018

8.6K

Related Concept Videos

Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
3.1K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
14.8K