Defective Ribonucleoproteins, Mistakes in RNA Processing, and Diseases

Abstract

Ribonucleoproteins (RNPs) are vital to many cellular events. To this end, many neurodegenerative diseases and cancers have been linked to RNP malfunction, particularly as this relates to defective processing of cellular RNA. The connection of RNPs and diseases has also propagated a shift of focus onto RNA targeting from traditional protein targeting treatments. However, therapeutic development in this area has been limited by incomplete molecular insight into the specific contributions of RNPs to disease. This review outlines the role of several RNPs in diseases, focusing on molecular defects in processes that affect proper RNA handling in the cell. This work also evaluates the contributions of recently developed methods to understanding RNP association and function. We review progress in this area by focusing on molecular malfunctions of RNPs associated with the onset and progression of several neurodegenerative diseases and cancer and conclude with a brief discussion of RNA-based therapeutic efforts.

RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

“…To this end, oxidative marks on RNA have been identified as an early indicator of cell death 17 , 23 , 28 . Damage to RNA induced by radicals could be detrimental to the cell, since RNA serves essential functions in protein synthesis, pathway regulation, and response to stress 29 . Compromise of these RNA functions could act as a modulating factor between oxidative stress and regulation of cellular pathways, potentially affecting the onset of disease.…”

“…The working concentration of 1 ppm formaldehyde represents a realistic, high exposure condition for occupational exposure 11 . Previous studies have used ALI exposures to study the effect of VOC mixtures 18 , 29 , 39 , 46 , cigarette smoke 47 , virus exposure 48 , and environmental pollutants 49 on lung cells. Overall, our work identifies differentially oxidized transcripts utilizing 8-oxoG RNA-immunoprecipitation coupled with RNA sequencing (8-oxoG RIP-seq) 39 .…”

Post-transcriptional air pollution oxidation to the cholesterol biosynthesis pathway promotes pulmonary stress phenotypes

“…Air pollution and cigarette smoke have been shown to cause accumulation of 8-oxoG RNA in epithelial A549 cells 17 and mouse lungs 18 , respectively. This is clinically relevant given that the abnormal accumulation of 8-oxoG modifications of RNAs has been shown in numerous diseases, including early neurodegeneration processes 19 and severe COPD 18 , suggesting a potential role of 8-oxoG in pathogenesis 20 .…”

Trajectories of RNA Virus Mutation Hidden by Evolutionary Alternate Reality Thermodynamic Endpoints in Transformations in Response to Abiotic Habitat Stresses

“…Each represents a characteristic frequency of a specific virus genome: the mutations are consistently carried by the thermodynamic moment of the habitat response to a stress, as the habitat system transitions from one alternate reality to the next. Where researchers traditionally describe mutations as mistakes [63], the lissajous thermodynamic model can disprove the assumption and demonstrate precisions in these genomic departures thorough transitions in alternate reality formation. Otherwise, in twodimension models, the enthalpic energy is represented by amplitudes S 0 1 and S 0 2 , generated by the periods T 1 and T 2 representing the process of transition from one evolutionary isenthalpic state to another future evolutionary state where energy of the habitat system is fully conserved; and that the delay ϕ facilitates the spread width and height for efficient distribution of the mutations necessary.…”