This 2017 article reviews evidence that pseudouridine may cause a number of pathologies, including cancer.
N1-methyl-pseudouridine, a modified nucleoside derived from pseudouridine, is an ingredient found in the Pfizer and Moderna mRNA Covid-19 vaccines. (source)
"Abstract
Pseudouridine is the most abundant modification found in RNA. Today, thanks to next-generation sequencing techniques used in the detection of RNA modifications, pseudouridylation sites have been described in most eukaryotic RNA classes. In the present review, we will first consider the available information on the functional roles of pseudouridine(s) in different RNA species. We will then focus on how alterations in the pseudouridylation process may be connected with a series of human pathologies, including inherited disorders, cancer, diabetes, and viral infections. Finally, we will discuss how the availability of novel technical approaches are likely to increase the knowledge in this field.
1. Introduction
A considerable number (>100) of different RNA modifications have been described. Of these, pseudouridine (Ψ) is the most frequent and the first to be discovered —more than 50 years ago. For these reasons it was named the 'fifth RNA nucleotide'...
4. Pseudouridine in Disease
The importance of Ψs in physiological processes may be better appreciated by taking a look at the other side of the same coin: pathology.
The first association ever reported between uridine modification and human disease was found in studies focusing on urinary metabolites in cancer patients. Ψ, like other modified nucleosides, cannot be recycled and is eliminated with urine; Ψ levels in urine mostly depend on the glomerular filtration rate and RNA turnover, and therefore are very often found to be higher in cancer patients. For this reason, the evaluation of urinary Ψs has been proposed as a potential tumor marker...
Two of the best examples of a disorder associated with a pseudouridylation defect are X-linked Dyskeratosis Congenita (X-DC) and its more severe form, Hoyeraal-Hreidarsson syndrome; these are two rare inherited syndromes caused by mutations in DKC1, the gene encoding for the pseudouridine synthase dyskerin... In addition to defects in proliferating tissues, one salient feature of X-DC is susceptibility to cancer...
In parallel to what has been found for dyskerin and pseudouridylation defects, we and other authors previously observed that, in human cancer, dyskerin expression and rRNA pseudouridylation levels may frequently be higher...
As described above, altered dyskerin pseudouridine synthase activity has been recognized as a potential trigger for cancer onset, in the case of both inherited syndrome-associated tumors and sporadic malignancies...
Recently, pseudouridylation has been implicated in other diseases, in addition to X-DC and cancer. Among these, Ψs have been recognized as regulators of viral latency processes in human immunodeficiency virus (HIV) infections...
Pseudouridylation has also been associated with the pathogenesis of maternally inherited diabetes and deafness (MIDD)...
In sum, different pseudouridine synthases are causative or participant in the onset of numerous diseases."
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).