ArticleExperimental & molecular medicine2024
Dichotomous intronic polyadenylation profiles reveal multifaceted gene functions in the pan-cancer transcriptome.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation.Genome research · 2026Article
- APAdeg enhances differentially expressed gene inference by leveraging site-specific signals in APA-seq data.Briefings in bioinformatics · 2026Article
- PolyA-GLM: A comprehensive framework forComputational and structural biotechnology journal · 2026Article
- E2-regulated transcriptome complexity revealed by long-read direct RNA sequencing: from isoform discovery to truncated proteins.RNA biology · 2025Article
- IPScan: Detecting novel intronic PolyAdenylation events with RNA-seq data.PLoS computational biology · 2025Article
- Regulation of transcriptome plasticity by mTOR signaling pathway.Experimental & molecular medicine · 2025Review
- Exploring transcriptome plasticity at the intersection of cell signaling, metabolism and computational biology.Experimental & molecular medicine · 2025Article
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Authors and funding
14 authors.
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Abstract
Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.
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