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.

FEBS Letters
|July 22, 2025
PubMed

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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