Abstract
Simple SummaryChronic hyperglycemia manifests in a variety of different micro- and macrovascular disorders such as diabetes mellitus and cardiovascular disease and has been shown to have links to post-transcriptional dysregulation. Equally, the development and progress of other devastating disorders such as tumorigenesis and neurodegenerative disease have also been associated with dysfunction of molecules involved in epigenetics such as RNA-binding proteins. Recent advances, especially on an analytical systemic level, have revealed new roles for these proteins and their contribution in maintaining the balance between normal function and dysfunction/disease.RNA-binding proteins (RBPs) are multi-faceted proteins in the regulation of RNA or its RNA splicing, localisation, stability, and translation. Amassing proof from many recent and dedicated studies reinforces the perception of RBPs exerting control through differing expression levels, cellular localization and post-transcriptional alterations. However, since the regulation of RBPs is reliant on the micro-environment and events like stress response and metabolism, their binding affinities and the resulting RNA-RBP networks may be affected. Therefore, any misregulation and disruption in the features of RNA and its related homeostasis can lead to a number of diseases that include diabetes, cardiovascular disease, and other disorders such as cancer and neurodegenerative diseases. As such, correct regulation of RNA and RBPs is crucial to good health as the effect RBPs exert through loss of function can cause pathogenesis. In this review, we will discuss the significance of RBPs and their typical function and how this can be disrupted in disease.
Highlights
RNA-binding proteins (RBPs) are critical RNA regulators responsible for modulating post-transcriptional events in the cell
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Small molecules can hinder RBP-RNA interaction by, for example, binding to RNA binding domain (RBD) such as in the case of small molecules targeting Eukaryotic Translation Initiation Factor 4E (eIF4E) [83]. Another anti-cancer strategy involves the use of an oligonucleotide-based strategy which includes short antisense oligonucleotides (ASOs), a few of which have previously been approved for the treatment of other diseases such as hyperlipidemias or viral infections [84]
Summary
RNA-binding proteins (RBPs) are critical RNA regulators responsible for modulating post-transcriptional events in the cell. RBPs can interact with target binding sites within the coding region to facilitate alternative splicing while RBP-RNA interactions within the 3 UTR domain can inhibit or induce mRNA decay, as well as mediate RNA stabilization. RBPs have key regulatory roles in important RNA maturation events such as polyadenylation, the addition of the 5 cap, and pre-mRNA alternative splicing, all of which are vital for the expression of functioning, mature RNA. Inducement of RNA stabilization and promotion of mRNA translation via binding to 3 UTR AREs. Cancer progression via differential splicing of cancer-relevant gene targets in MDS. Involvement in SMA by increasing FUBP1 affinity to SNF1 pre-mRNA
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