Biochemistry & Molecular Biology Journal Open Access

RNA Splicing Dysregulation: A Key Player in Disease Development

Hans Nikawa^* Department of Pharmaceutics, University of Alfaisal, Saudi Arabia
^*Correspondence: Hans Nikawa, Department of Pharmaceutics, University of Alfaisal, Saudi Arabia, Email:

Received: 31-Jul-2024, Manuscript No. IPBMBJ-24-21594; Editor assigned: 02-Aug-2024, Pre QC No. IPBMBJ-24-21594 (PQ); Reviewed: 16-Aug-2024, QC No. IPBMBJ-24-21594; Revised: 21-Aug-2024, Manuscript No. IPBMBJ-24-21594 (R); Published: 28-Aug-2024, DOI: 10.36648/2471-8084-10.04.37

Introduction

RNA splicing is a fundamental cellular process that involves the removal of non-coding regions (introns) from precursor messenger RNA and the joining of coding regions (exons) to produce mature mRNA. This mature mRNA is then translated into proteins, which carry out various essential functions within the cell. However, dysregulation of RNA splicing can have profound consequences, leading to a range of diseases, including cancer, neurodegenerative disorders, and genetic syndromes. This article explores the mechanisms of RNA splicing dysregulation, its impact on disease, and the potential for therapeutic interventions. RNA splicing is carried out by a complex molecular machine known as the spliceosome. This multi-protein and RNA complex recognizes specific sequences at the exon-intron boundaries and facilitates the precise removal of introns. The process involves several key steps: The recognition of splice sites, the formation of the spliceosome complex, and the ligation of exons.

Description

Splice Site Recognition: Sequence elements at exon-intron boundaries, such as the 5’ splice site, branch point, and 3’ splice site, are recognized by the spliceosome. Alternative Splicing: Cells can produce multiple mRNA isoforms from a single gene through alternative splicing, which allows for the generation of diverse protein isoforms with distinct functions. Dysregulation of RNA splicing can arise from various mechanisms, including genetic mutations, epigenetic changes, and alterations in splicing regulatory proteins. These disruptions can lead to the production of aberrant mRNA isoforms and contribute to disease pathology. Mutations in the genes encoding splicing factors or within the premRNA itself can disrupt normal splicing. For example, mutations in the spliceosome components or splicing regulatory elements can lead to exon skipping, intron retention, or the inclusion of cryptic exons. Such mutations are implicated in several genetic disorders, including: Epigenetic modifications, such as DNA methylation and histone modifications, can influence splicing regulation by altering the accessibility of splicing regulatory elements or affecting the binding of splicing factors. Aberrant epigenetic regulation can lead to inappropriate splicing and contribute to cancer development. For example, aberrant splicing of genes involved in cell cycle regulation can lead to uncontrolled cell proliferation. Changes in the expression levels or activity of splicing factors can disrupt normal splicing patterns. For instance, overexpression or misregulation of SR proteins or hnRNPs can lead to the generation of abnormal mRNA isoforms. This dysregulation is often observed in cancer, where altered splicing contributes to tumorigenesis by producing variants that drive cancer cell proliferation or metastasis. Splicing dysregulation is implicated in several neurodegenerative diseases. In Alzheimer’s disease, for example, alternative splicing of the tau protein can produce isoforms that aggregate and form neurofibrillary tangles, contributing to neurodegeneration. Inherited genetic syndromes often involve splicing defects. For instance, the splice site mutation in the CFTR gene causes cystic fibrosis by disrupting the correct splicing of the CFTR mRNA, leading to defective chloride channels and resulting in severe respiratory and digestive issues.

Conclusion

Future research in splicing dysregulation will focus on understanding the complex interactions between splicing factors, regulatory elements, and disease mechanisms. Advancements in high-throughput sequencing and computational tools will enhance our ability to identify and characterize splicing abnormalities. Additionally, the development of novel therapeutic approaches, including precision medicine and personalized therapies, holds promise for addressing splicing-related diseases more effectively. In conclusion, RNA splicing dysregulation plays a critical role in various diseases, including cancer, neurodegenerative disorders, and genetic syndromes. By unraveling the mechanisms underlying splicing abnormalities and exploring targeted therapeutic strategies, researchers are making significant strides towards improving diagnosis, treatment, and patient outcomes. Continued research and innovation in this field will be essential for advancing our understanding of splicing dysregulation and developing effective interventions for a range of diseases.