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Hydrolytic nucleoside and nucleotide deamination, and genetic instability: a possible link between RNA-editing
Shrikant Anant1, Nicholas O Davidson
1Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Abstract:
Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RNAs, and each requires distinctive enzymatic machinery. Alterations in the expression or abundance of RNA-editing factors produce unanticipated alterations in the processing or expression of RNAs, in some cases outside their physiological targets. Recent findings suggest that unregulated expression of the cytidine-deaminase gene family might lead to deamination of deoxycytidine nucleotides in DNA. Aberrant or dysregulated RNA editing, or altered expression of editing factors, might contribute to genomic instability in cancer.
Insights
RNA editing modifies gene products via enzymatic deamination. Dysregulation of RNA editing factors may cause genomic instability and cancer by affecting DNA and RNA.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Post-transcriptional RNA editing alters gene products by changing transcript sequences from the genome.
- Mammalian RNA editing involves two classes of enzymatic deamination with specific requirements.
- Distinct enzymatic machinery is needed for each class of RNA editing.
Purpose of the Study:
- To explore the consequences of altered RNA editing factor expression.
- To investigate the link between RNA editing dysregulation and genomic instability in cancer.
Main Methods:
- Analysis of RNA editing processes and enzymatic deamination.
- Examination of the effects of altered expression of RNA-editing factors.
- Investigation into potential DNA deamination by cytidine deaminases.
Main Results:
- Altered expression of RNA-editing factors can lead to unintended RNA processing and expression changes.
- Unregulated cytidine deaminase expression may cause deoxycytidine deamination in DNA.
- Aberrant RNA editing or altered editing factor expression may contribute to genomic instability.
Conclusions:
- RNA editing is a critical process with significant implications when dysregulated.
- Altered RNA editing factors may impact both RNA and DNA integrity.
- RNA editing dysregulation is a potential contributor to cancer development and genomic instability.