Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

RNA modifications by oxidation: A novel disease mechanism?

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Interventions targeted at oxidatively generated modifications of nucleic acids focused on urine and plasma markers

    Research output: Contribution to journalReviewResearchpeer-review

  2. Oxidatively generated modifications to nucleic acids in vivo: Measurement in urine and plasma

    Research output: Contribution to journalReviewResearchpeer-review

  3. The Effect of Different Training Intensities on Oxidatively Generated Modifications of Nucleic Acids: A Randomized, Controlled Trial

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  4. RNA oxidation and iron levels in patients with diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Two-fold risk of pneumonia and respiratory mortality in individuals with myeloproliferative neoplasm: A population-based cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Estimates of prediabetes and undiagnosed type 2 diabetes in Denmark: The end of an epidemic or a diagnostic artefact?

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

    Research output: Contribution to journalReviewResearchpeer-review

View graph of relations
The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes, but the oxidation results in ribosomal stalling and dysfunction, followed by decreased levels of functional protein as well as the production of truncated proteins that do not undergo proper folding and may result in protein aggregation within the cell. Ribosomal dysfunction may also signal apoptosis by p53-independent pathways. There are very few reports on interventions that reduce RNA oxidation, one interesting observation being a reduction in RNA oxidation by ingestion of raw olive oil. High urinary excretion of 8-oxo-guanosine, a biomarker for RNA oxidation, is highly predictive of death in newly diagnosed type 2 diabetics; this demonstrates the clinical relevance of RNA oxidation. Taken collectively the available data suggest that RNA oxidation is a contributing factor in several diseases such as diabetes, hemochromatosis, heart failure, and β-cell destruction. The mechanism involves free iron and hydrogen peroxide from mitochondrial dysfunction that together lead to RNA oxidation that in turn gives rise to truncated proteins that may cause aggregation. Thus RNA oxidation may well be an important novel contributing mechanism for several diseases.
Original languageEnglish
JournalFree Radical Biology & Medicine
Volume52
Issue number8
Pages (from-to)1353-61
Number of pages9
ISSN0891-5849
DOIs
Publication statusPublished - 2012

ID: 34768985