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Noncoding Centromeric RNA Expression Impairs Chromosome Stability in Human and Murine Stem Cells.
David Y L Chan1,2, Daniela Moralli1, Suhail Khoja1
1Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Disease Markers
|August 8, 2017
Summary
Overexpressing centromeric satellites, a type of noncoding RNA, causes chromosome mis-segregation and genomic instability in human and mouse cells. This suggests their potential as cancer biomarkers.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Centromeric noncoding RNAs are detected in various carcinoma cells.
- Their role in genomic instability and chromosome segregation remains under investigation.
Purpose of the Study:
- To investigate the impact of transcribed noncoding RNA centromeric satellites on chromosome segregation.
- To explore the potential of these RNAs as biomarkers for neoplastic cells.
Main Methods:
- Analyzing chromosome segregation in normal human and murine stem and fibrosarcoma cells.
- Overexpressing different centromeric alphoid DNAs and mouse minor satellite DNA.
- Utilizing live cell imaging to observe chromosomal morphological errors.
- Examining chromosome segregation in vivo.
Main Results:
- Overexpression of centromeric alphoid DNAs increased chromosome mis-segregation in all tested cell lines.
- Overexpression of mouse minor satellite increased chromosome instability in murine stem cells but not human cells.
- In vivo analysis revealed disturbances in mitotic progression.
- Live imaging showed various chromosomal morphological errors in cell nuclei upon satellite overexpression.
Conclusions:
- Transcribed noncoding RNA centromeric satellites contribute to genomic instability by causing chromosome segregation errors.
- These findings provide insights into a novel source of genomic instability in human and murine cells.
- Overexpression of centromeric noncoding RNAs may serve as specific markers for neoplastic cells.
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