RNA‐binding proteins in diabetic microangiopathy

Abstract

Dynamic RNPs (ribonucleoprotein particles) are formed when RNAbinding proteins assemble with RNA. RNP compositions vary depending on the maturation or the functional state of the RNA as well as the cell environment. [1][2][3] All aspects of RNA life, including splicing, transcription, intracellular trafficking, modification, translation, as well as decay, are regulated by RBPs. In turn, RNA can modulate the location or activity of RBPs through a process called "riboregulation." 4 The PRK (protein kinase R) induces autophosphorylation and dimerization of proteins through their binding to double-stranded RNA, which activates the enzyme and is a prime example of riboregulation (Figure 1). 5 RBP dysfunction and dysregulation are correlated to several muscular atrophies and neurological disorder diseases in humans, like amyotrophic lateral sclerosis, 6 cancer, 7 and genetic abnormalities. 8 RBPs are conserved evolutionarily and have a wide distribution in tissues, in line with their common roles concerning housekeeping. In spite of these attributes, alterations or mutations in RBPs responsible for housekeeping can often lead to specific tissue defects.How does this occur? First, RBPs possibly act on their RNA targets or regulatory partners that express tissue specificity. Secondly, RBPs may attach to RNA targets with various specificities and affinities, regulated by modifications in RNA post-translation, their interactions, and local structure or sequence, causing regulatory complex formation to specific cell types. 9-12 Third, attachment of RNA by itself may not always lead to regulatory effects. Even though RBPs are capable of binding hundreds of RNA targets, only some of them are regulated in particular cellular conditions. In RNA regulons, a set of RNAs are coordinated and regulated by a given RBP under the influence of stimuli. 13,14 Finally, the RBPs cause the formation of extensive network structures with their RNA targets and other

RNA-binding proteins potentially regulate the alternative splicing of cell cycle-associated genes in proliferative diabetic retinopathy

“…RBPs are involved in complex interrelated molecular mechanisms of PDR, suggesting their potential as therapeutic targets for PDR 27 . Overexpression of the RBP lin-28 homolog B could exacerbate angiogenesis and elevate the protein levels of proangiogenic factors in human retinal endothelial cells and human retinal microvascular endothelial cells 28 .…”

Web tools support predicting protein–nucleic acid complexes stability with affinity changes

“…With 20,500 proteins coding for genes by humans, they confirmed that 7.5% are linked to RNA metabolism through the binding and processing of RNA or forming significant parts of RNPs (Gerstberger et al, 2014). Cellular dysfunctions and human illnesses, such as neurological disease (Chen et al, 2021; Hao et al, 2016; Propson et al, 2021), immunodeficiency disease (Iritani, 2021), Parkinson's disease (Olsen & Feany, 2019), and cancer (Halbach et al, 2017), are linked to aberrant protein–nucleic acid interaction (Tu et al, 2022). Therefore, understanding the recognition mechanisms of protein–nucleic acids is critical to strengthen our knowledge of the complex pathogenic mechanisms (Valeur et al, 2017; Y.‐L.…”

“…illnesses, such as neurological disease (Chen et al, 2021;Hao et al, 2016;Propson et al, 2021), immunodeficiency disease (Iritani, 2021), Parkinson's disease (Olsen & Feany, 2019), and cancer (Halbach et al, 2017), are linked to aberrant protein-nucleic acid interaction (Tu et al, 2022). Therefore, understanding the recognition mechanisms of proteinnucleic acids is critical to strengthen our knowledge of the complex pathogenic mechanisms (Valeur et al, 2017;Wu et al, 2018;Yu et al, 2020).…”