DES-ROD: Exploring Literature to Develop New Links between RNA Oxidation and Human Diseases

Abstract

Normal cellular physiology and biochemical processes require undamaged RNA molecules. However, RNAs are frequently subjected to oxidative damage. Overproduction of reactive oxygen species (ROS) leads to RNA oxidation and disturbs redox (oxidation-reduction reaction) homeostasis. When oxidation damage affects RNA carrying protein-coding information, this may result in the synthesis of aberrant proteins as well as a lower efficiency of translation. Both of these, as well as imbalanced redox homeostasis, may lead to numerous human diseases. The number of studies on the effects of RNA oxidative damage in mammals is increasing by year due to the understanding that this oxidation fundamentally leads to numerous human diseases. To enable researchers in this field to explore information relevant to RNA oxidation and effects on human diseases, we developed DES-ROD, an online knowledgebase that contains processed information from 298,603 relevant documents that consist of PubMed abstracts and PubMed Central full-text articles. The system utilizes concepts/terms from 38 curated thematic dictionaries mapped to the analyzed documents. Researchers can explore enriched concepts, as well as enriched pairs of putatively associated concepts. In this way, one can explore mutual relationships between any combinations of two concepts from used dictionaries. Dictionaries cover a wide range of biomedical topics, such as human genes and proteins, pathways, Gene Ontology categories, mutations, noncoding RNAs, enzymes, toxins, metabolites, and diseases. This makes insights into different facets of the effects of RNA oxidation and the control of this process possible. The usefulness of the DES-ROD system is demonstrated by case studies on some known information, as well as potentially novel information involving RNA oxidation and diseases. DES-ROD is the first knowledgebase based on text and data mining that focused on the exploration of RNA oxidation and human diseases.

RNA and Oxidative Stress in Alzheimer’s Disease: Focus on microRNAs

“…It remains to be determined whether there exists a common motif and sequence for the selective oxidation of miRNAs [19]. Although oxidized miRNAs are not identified in the human brain diseases at the current moment, possible involvement of the oxidized miRNAs in AD and related neurodegeneration is strongly suggested [8,44,45]. Additionally, direct oxidative modifications to other noncoding RNAs such as small nuclear RNAs, small nucleolar RNAs, long noncoding RNAs, and circular RNAs are not reported, while the role of these RNA species in the nervous system has recently drawn growing attention [46,47].…”

Role of RNA Oxidation in Neurodegenerative Diseases

“…Therefore, oxidative damage of protein-coding RNA or non-coding RNA can affect the gene expression. Although RNA oxidation is not as fatal as genomic mutations, RNA oxidative damage is a typical feature of neuronal fragility, suggesting that RNA oxidation may promote the occurrence of chronic degeneration [ 4 , 5 ], including Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy body dementia, and prion diseases [ 6 ]. Increasing research evidence that preventing damaged nucleotides play a role in translation can significantly reduce the harmful effects of oxidative RNA on protein synthesis.…”