Abstract
RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5’ and 3’ splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.
Highlights
RNA splicing is regulated by a number of factors that determine gene expression and function, and is closely related to the transcriptional machinery involved in RNA polymerase (RNAP) II, translational processes, and epigenetic processes associated with chromatin status
These results suggest that the modulated expression of guide sno/scaRNAs can be linked to snRNA activation in cancer
The introns associated with the creation of new exons were predominantly larger than the genome-wide mean intron length, and splicing changes induced by non-coding mutations were observed in cancer-related genes such as ATRX, BCOR, CDKN2B, MAP3K1, MAP3K4, MDM2, SMAD4, STK11, and TP53, leading to truncated protein production and gene expression alteration [73]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Previous studies have revealed that RNA splicing is essential for mRNA maturation and regulation of gene expression. Alternative splicing generates multiple mRNAs from a limited number of genes, leading to the synthesis of a variety of proteins and functional diversity. This process plays an important role in cell differentiation and development. RNA splicing is regulated by a number of factors that determine gene expression and function, and is closely related to the transcriptional machinery involved in RNA polymerase (RNAP) II, translational processes, and epigenetic processes associated with chromatin status. Cancer-related mis-splicing affects gene expression levels and the transcriptional machinery, epigenome, and downstream signaling pathways for cancer survival. This review discusses recent studies on aberrant alternative splicing associated with cancer and the targeted therapeutic methods
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