RNA, like DNA, is susceptible to damage from various sources, both internal (endogenous) and external (exogenous). Understanding these damaging agents is crucial for comprehending cellular processes and developing effective therapeutic strategies.
Types of RNA Damage
Several factors contribute to RNA damage, leading to alterations in its structure and function:
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Ultraviolet (UV) irradiation: UV light, especially UVB radiation from the sun, causes significant RNA damage. This includes photochemical modifications, crosslinking, and oxidative damage to the RNA molecule. ([Reference: Ultraviolet (UV) irradiation can cause several types of damage to RNA: photochemical modification, crosslinking, and oxidative damage]) UV damage is implicated in sunburn, aging, and carcinogenesis. ([Reference: Exposure to ultraviolet B (UVB) radiation from the sun can result in sunburn, premature aging and carcinogenesis, but the mechanism…])
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Oxidation: Reactive oxygen species (ROS) produced during normal metabolism or environmental stress can oxidize RNA bases, altering their structure and potentially disrupting RNA function. ([Reference: Here, we begin by reviewing the most abundant types of chemical damage to RNA, including oxidation and alkylation.])
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Alkylation: Alkylating agents add alkyl groups to RNA bases, again leading to structural changes and functional impairment. ([Reference: Here, we begin by reviewing the most abundant types of chemical damage to RNA, including oxidation and alkylation.])
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Chlorination and Nitration: These chemical modifications, often caused by environmental pollutants or endogenous processes, can alter RNA structure and function. ([Reference: Damage to RNA from ultraviolet light, oxidation, chlorination, nitration, and akylation can include chemical modifications to nucleobases as well as RNA-RNA…])
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Exogenous Agents: Therapeutic drugs and other external agents can also damage RNA. ([Reference: RNA is damaged by both endogenous and exogenous agents, with the effect of exogenous agents administered as therapeutics the focus of this review.]) One example is 5-fluorouracil (5-FU), a chemotherapy drug where RNA damage plays a significant role in its efficacy. ([Reference: We unexpectedly found that an RNA damage response during ribosome biogenesis dominates the drug's efficacy in tumor types for which 5-FU shows clinical benefit.])
Cellular Response to RNA Damage
Cells have developed mechanisms to handle RNA damage, including:
- Compartmentalization: Damaged RNA can be sequestered into specific cellular compartments like stress granules to prevent further damage or interference with cellular processes. ([Reference: Here, we identified a distinct stress granule (SG), marked by dsRNA helicase DHX9, which compartmentalizes ultraviolet (UV)-induced RNA, but not DNA, damage.])
- Repair Mechanisms: While less understood than DNA repair, cells do possess mechanisms to repair some types of RNA damage. ([Reference: Some forms of environmental stress, such as exposure to oxidants and ultraviolet light, result in RNA damage, yet little is known of how damaged…])
Conclusion
Understanding the various factors that damage RNA is crucial for advancements in various fields, including medicine and environmental science. Further research is needed to fully elucidate the cellular response and repair mechanisms associated with RNA damage.
