Related Experiment Video

Updated: Apr 2, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

9.5K

Splicing factor TRA2B enhances synthesis of androgen receptor variant AR-V7 in prostate cancer cells

Nicholas Brittain1, Alec Paschalis2,3, Ryan Nelson1

  • 1Newcastle University Centre for Cancer, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne, United Kingdom.

The Journal of Clinical Investigation
|April 1, 2026
PubMed

Insights

Researchers identified TRA2B and TRA2A as key regulators in prostate cancer (PC) progression. These splicing factors promote the synthesis of androgen receptor variants (AR-Vs), driving treatment resistance in castrate-resistant PC (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (PC) treatments targeting the androgen receptor (AR) have limited durability, often leading to castrate-resistant PC (CRPC).
  • Constitutively active AR splice variants (AR-Vs), like AR-V7, are crucial drivers of treatment resistance and disease progression in advanced PC.
  • Understanding the mechanisms of AR-V generation is critical for developing new therapeutic strategies against treatment-resistant prostate cancer.

Purpose of the Study:

  • To identify protein interactors of AR-V7 mRNA using an RNA-targeting CasRx system.
  • To elucidate the role of identified factors in AR-V synthesis and their impact on PC cell growth.

Main Methods:

  • Utilized an RNA-targeting CasRx approach to screen for AR-V7 mRNA interacting proteins in prostate cancer cells.
  • Investigated the function of identified splicing regulators (TRA2B, TRA2A) in AR transcript splicing and AR-V generation.
  • Correlated TRA2B expression with AR-V7 transcript levels in CRPC patient samples.

Main Results:

  • Identified TRA2B and TRA2A as key splicing regulators that promote AR-V synthesis over full-length AR isoforms.
  • Demonstrated that TRA2B expression correlates with AR-V7 transcript levels in CRPC.
  • Showed that inhibiting TRA2-mediated splicing significantly reduced prostate cancer cell growth.

Conclusions:

  • TRA2B and TRA2A are critical mediators of AR-V production, contributing to treatment resistance in advanced prostate cancer.
  • Targeting TRA2-mediated splicing represents a potential therapeutic strategy for overcoming resistance in castrate-resistant prostate cancer.
  • Further investigation into TRA2B function may unlock novel therapeutic opportunities for patients with advanced prostate cancer.
Keywords:
Clinical ResearchOncologyProstate cancer

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.7K
Using the E1A Minigene Tool to Study mRNA Splicing Changes10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

5.6K

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
61.4K
RNA Splicing01:32

RNA Splicing

20.3K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
26.6K
Alternative RNA Splicing02:18

Alternative RNA Splicing

5.5K
Pre-mRNA Processing: RNA Splicing01:36

Pre-mRNA Processing: RNA Splicing

7.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
69