Alternative splicing and related RNA binding proteins in human health and disease

Abstract

Alternative splicing (AS) serves as a pivotal mechanism in transcriptional regulation, engendering transcript diversity, and modifications in protein structure and functionality. Across varying tissues, developmental stages, or under specific conditions, AS gives rise to distinct splice isoforms. This implies that these isoforms possess unique temporal and spatial roles, thereby associating AS with standard biological activities and diseases. Among these, AS-related RNA-binding proteins (RBPs) play an instrumental role in regulating alternative splicing events. Under physiological conditions, the diversity of proteins mediated by AS influences the structure, function, interaction, and localization of proteins, thereby participating in the differentiation and development of an array of tissues and organs. Under pathological conditions, alterations in AS are linked with various diseases, particularly cancer. These changes can lead to modifications in gene splicing patterns, culminating in changes or loss of protein functionality. For instance, in cancer, abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes, thereby promoting the onset and progression of tumors. AS and RBPs are also associated with numerous neurodegenerative diseases and autoimmune diseases. Consequently, the study of AS across different tissues holds significant value. This review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases, which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

RNA-binding proteins in bone pathophysiology

“…In eukaryotic, alternative splicing guarantees the generation of different pre-RNAs from the same gene, contributing to both transcriptome and proteome complexity ( Wang et al, 2015 ; Tao et al, 2024 ). At molecular level, this process is guaranteed by an important macromolecular complex, the spliceosome, and a combination of several proteins, which cooperate to regulate a series of RNA-RNA and RNA-protein interactions ( Tao et al, 2024 ).…”

“…In eukaryotic, alternative splicing guarantees the generation of different pre-RNAs from the same gene, contributing to both transcriptome and proteome complexity ( Wang et al, 2015 ; Tao et al, 2024 ). At molecular level, this process is guaranteed by an important macromolecular complex, the spliceosome, and a combination of several proteins, which cooperate to regulate a series of RNA-RNA and RNA-protein interactions ( Tao et al, 2024 ). In general, by binding regulatory sequence elements of pre-mRNAs, hnRNP can act as either an activator or repressor of spliceosome recruitment, promoting or suppressing the inclusion of an exon, thus contributing to the generation of different mRNA transcripts ( Horn et al, 2023 ).…”