RPS24 alternative splicing - is a marker of cancer progression and epithelial-mesenchymal transition

Sep 21, 2026

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Alternative splicing (AS) generates transcript diversity, yet the mechanisms driving variability in ribosomal proteins remain insufficiently understood. This study analyzes ribosomal protein S24 (RPS24) AS isoforms by resolving splice junctions involving three microexons. Four AS isoforms show tissue specificity and distinct expression patterns across cancer types, with cancer-versus-normal differences in isoform proportions. The work identifies a correlation between a specific RPS24 isoform and epithelial–mesenchymal transition in lung and breast cancers.

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Definition and classification of RPS24 AS isoforms

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN RPS24 alternative splicing is a marker of cancer progression and epithelial‑mesenchymal transition Jiyeon Park1, Da Hae Nam2, Dokyeong Kim1,3 & Yeun‑Jun Chung1,2,4* Although alternative splicing (AS) is a major mechanism that adds diversity to gene expression patterns, its precise role in generating variability in ribosomal proteins, known as ribosomal heterogeneity, remains unclear. The ribosomal protein S24 (RPS24) gene, encoding a ribosomal component, undergoes AS; however, in‑depth studies have been challenging because of three microexons between exons 4 and 6. We conducted a detailed analysis of RPS24 AS isoforms using a direct approach to investigate the splicing junctions related to these microexons, focusing on four AS isoforms. Each of these isoforms showed tissue specificity and relative differences in expression among cancer types. Significant differences in the proportions of these RPS24 AS isoforms between cancerous and normal tissues across diverse cancer types were also observed. Our study highlighted a significant correlation between the expression levels of a specific RPS24 AS isoform and the epithelial– mesenchymal transition process in lung and breast cancers. Our research contributes to a better understanding of the intricate regulatory mechanisms governing AS of ribosomal protein genes and highlights the biological implications of RPS24 AS isoforms in tissue development and tumorigenesis. Keywords Ribosomal protein genes, Ribosome, RPS24, Microexon, Epithelial–mesenchymal transition Ribosomes, which consist of ribosomal proteins and ribosomal RNAs, are the cellular machinery responsible for translation. Despite their vital role in protein synthesis, recent discoveries have revealed their heterogeneity across tissues and disease conditions1,2. With the advances in genome technology enabling an in-depth understanding of transcriptional and translational processes, specialized roles of heterogeneous ribosomes in cancer progression and therapeutic resistance have been uncovered3,4. Systematic investigations have been conducted to study the functional impact of each ribosomal component using transcriptional and translational profiling5,6. Recent studies using large-scale proteomics data have revealed a poor correlation between the mRNA and protein expression levels of genes encoding ribosomal proteins, implicating the significance of post-transcriptional regulation in ribosome biogenesis7,8. Alternative splicing (AS) is a post-transcriptional regulatory process that allows a single gene to encode multiple transcripts. AS is an important source of gene expression heterogeneity that leads to phenotypic diversity9. Genome-wide AS studies have been promoted with large-scale sequencing projects such as The Cancer Genome Atlas (TCGA)10, 11. Recently, the role ofAS in ribosomal heterogeneity has gained attention. A single-cell study identified cell type-specific regulation of AS events in ubiquitously expressed genes, including the ribosomal protein S24 (RPS24) 12. A recent study showed that AS can modulate ribosomal composition in glioblastoma cells, suggesting the prognostic and therapeutic value of AS in the ribosomal protein L22-like1 (RPL22L1) gene13. These studies suggest that AS is an important source of ribosomal heterogeneity. We recently developed a pan-cancer database of AS events for the molecular classification of cancers (ASCMC)14. Within this repository, RPS24 AS is one of the most notable AS events, displaying subtype-specific differences across multiple cancer types. However, the details ofthe RPS24S AS event remain elusive due to the involvement of three microexons, which have been overlooked in AS research because of their small size (3–30 1Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 137-701, Republic of Korea. 2Department of

FAQs

Why is RPS24 alternative splicing difficult to study?

RPS24 AS involves three microexons between exons 4 and 6, which are small and have been overlooked, making detailed junction analysis challenging.

What patterns do the four RPS24 AS isoforms show across tissues and cancers?

Each isoform exhibits tissue specificity and relative expression differences among cancer types, and their proportions differ significantly between cancerous and normal tissues across diverse cancers.

How is RPS24 AS linked to epithelial–mesenchymal transition (EMT)?

A specific RPS24 AS isoform’s expression level correlates with the EMT process in lung and breast cancers, and the relevance of the isoform is validated using experimental data.

Sep 21, 2026

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