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Updated: Sep 14, 2025

Adapting 3' Rapid Amplification of CDNA Ends to Map Transcripts in Cancer
Published on: March 28, 2018
The 3' end of the tale-neglected isoforms in cancer
Didem Naz Dioken1, Ibrahim Ozgul1, Ayse Elif Erson-Bensan1,2
1Department of Biological Sciences, Middle East Technical University, Ankara, Türkiye.
Abstract:
The evolutionary expansion of 3' untranslated regions (3'UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3'UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA-binding proteins and non-coding RNAs, thereby contributing to cell-type-specific and context-dependent gene expression. Mounting evidence highlights the importance of non-coding regions, particularly 3'UTRs, in normal physiology and disease states, including cancer. Genomic alterations and driver mutations in coding regions play a well-established role in cancer biology. Advances in long-read sequencing and 3'UTR-focused genome-/transcriptome-wide association studies (GWAS/TWAS) improve our understanding of transcriptome complexity and how mRNA isoforms with different 3'-ends may impact protein functions. This Review explores the regulatory roles of 3'UTRs, sources of 3'UTR isoform diversity, and implications in cancer, emphasizing the need for further research into their diagnostic and therapeutic potential. Impact statement This review highlights how alternative polyadenylation generates diverse mRNA 3'-end isoforms in cancer. Isoforms with distinct 3'UTRs are differentially regulated by microRNAs and RNA-binding proteins, while intronically polyadenylated isoforms can lead to C-terminally truncated proteins with altered functions.
Insights
Alternative polyadenylation generates diverse messenger RNA (mRNA) 3'-end isoforms in cancer. These distinct 3' untranslated regions (3'UTRs) impact gene expression and protein function, offering potential diagnostic and therapeutic targets.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- 3' untranslated regions (3'UTRs) regulate gene expression through interactions with RNA-binding proteins and non-coding RNAs.
- 3'UTRs are crucial for mRNA stability, translation, and localization, contributing to cell-type-specific gene expression.
- Non-coding regions, especially 3'UTRs, are increasingly recognized for their roles in normal physiology and disease, including cancer.
Purpose of the Study:
- To review the regulatory roles of 3'UTRs in gene expression.
- To explore the sources of 3'UTR diversity, including alternative polyadenylation (APA).
- To discuss the implications of 3'UTR alterations in cancer and their diagnostic/therapeutic potential.
Main Methods:
- Review of existing literature on 3'UTRs, APA, and cancer biology.
- Integration of findings from genomic and transcriptomic studies, including long-read sequencing and GWAS/TWAS.
- Analysis of how 3'UTR isoforms affect gene regulation and protein function.
Main Results:
- Alternative polyadenylation generates diverse mRNA 3'-end isoforms with distinct 3'UTRs.
- These isoforms are differentially regulated by microRNAs and RNA-binding proteins.
- Intronically polyadenylated isoforms can produce C-terminally truncated proteins with altered functions.
Conclusions:
- 3'UTR diversity, driven by APA, plays a significant role in cancer development and progression.
- Understanding these isoforms is critical for deciphering cancer biology.
- Further research into 3'UTRs holds promise for novel cancer diagnostics and therapeutics.
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