RNA-Binding Proteins Hold Key Roles in Function, Dysfunction, and Disease

Abstract

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.

Myoparr-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation

“…RBPs have multiple molecular functions including RNA splicing, transcription, translation, RNA stability, and the formation of the nuclear structure to regulate cell proliferation, differentiation, development, and diseases [ 14 ]. Although many RBPs have multiple functions in the cells [ 15 , 16 , 17 ], it is still unclear how their pleiotropic functions are determined.…”

“…A ubiquitously expressed RBP, known as human antigen R (HuR), associates with lncRNAs and regulates their stability; HuR increases the cytosolic linc-MD1 levels in skeletal muscle cells [ 12 ], whereas it promotes the decay of lincRNA-p21 in HeLa cells [ 13 ]. Additionally, RBPs are also involved in RNA splicing, polyadenylation, RNA transport, and translation [ 14 ]. The majority of RBPs are involved in multiple biological processes in concert with lncRNAs [ 15 , 16 , 17 ], and mutations in genes coding for RBPs are associated with human genetic disorders [ 18 ].…”

RNA Modifications and RNA Metabolism in Neurological Disease Pathogenesis

“…Expression-mediated RBP functions may be countered by other RBPs, thereby maintaining a balance of RNA metabolism and gene expression for neurons in different parts of the brain. Dysregulated RBP functioning and enrichment can severely perturb such control mechanisms, resulting in neurodevelopmental or neurodegenerative diseases (summarized in Table 1) [111,112].…”

The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians

“…In particular, alternative splicing, in which an exon or intron is either excluded from or included in a transcript, has the potential to greatly expand both transcriptomic and proteomic diversity [ 18 – 20 ]. RNA-binding proteins mediate much of this posttranscriptional regulation, with the same proteins often regulating multiple aspects of RNA metabolism [ 21 , 22 ]. Targeting of RNA by these regulators is usually mediated by RNA-binding domains [ 23 ], which are typically discrete and ordered.…”