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Published on: September 20, 2021
RNA splicing: a new player in the DNA damage response
Silvia C Lenzken1, Alessia Loffreda, Silvia M L Barabino
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milan, Italy.
Abstract:
It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.
Insights
RNA processing, including pre-mRNA splicing, is a newly identified pathway crucial for maintaining genome stability. Splicing factors play a role in the DNA damage response (DDR), which in turn affects splicing activity.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Tumorigenesis involves sequential genetic alterations, but the molecular basis of genomic instability remains incompletely understood.
- Accumulation of DNA damage, often due to mutations in DNA repair and checkpoint genes in hereditary cancers, is a significant driver of oncogenic transformation.
- Identifying cellular pathways involved in DNA damage response is critical for understanding cancer development.
Purpose of the Study:
- To review the emerging role of RNA processing, specifically pre-mRNA splicing, in maintaining genome stability.
- To elucidate the interplay between splicing factors and the DNA damage response (DDR).
Main Methods:
- Literature review focusing on molecular mechanisms linking RNA processing and genome stability.
- Analysis of the role of splicing factors in cellular responses to DNA damage.
- Examination of how DDR activation impacts splicing factor activity.
Main Results:
- Pre-mRNA splicing represents a novel pathway contributing to genome stability.
- Splicing factors are involved in the DNA damage response.
- Activation of the DNA damage response can modulate the activity of splicing factors.
Conclusions:
- The interaction between RNA processing and genome stability is a significant area of cancer research.
- Understanding these mechanisms may reveal new therapeutic targets for cancer treatment.
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