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Updated: Jun 30, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing associated with therapeutic response to

Carolyn M Jablonowski1, Waise Quarni1, Shivendra Singh1

  • 1Department of Surgery, St Jude Children's Research Hospital, Memphis, United States.

Elife
|March 15, 2024
PubMed

Insights

JMJD6 connects pre-mRNA splicing and metabolism in MYC-driven cancers. Targeting JMJD6 may offer new therapies for neuroblastoma by impacting glutamine metabolism and splicing.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYC-driven cancers exhibit dysregulated pre-mRNA splicing and metabolism.
  • Therapeutic strategies targeting these processes are under investigation.
  • The interplay between splicing and metabolism under oncogenic stress remains unclear.

Purpose of the Study:

  • To investigate the role of JMJD6 in connecting pre-mRNA splicing and metabolism in MYC-driven neuroblastoma.
  • To elucidate how JMJD6 influences cellular transformation and metabolic pathways in response to oncogenic stress.

Main Methods:

  • Investigated JMJD6 interactions with MYC and RNA-binding proteins.
  • Analyzed JMJD6's control over glutaminase (GLS) alternative splicing.
  • Assessed the correlation between JMJD6, indisulam, and cancer cell killing.

Main Results:

  • JMJD6 acts as a hub linking splicing and metabolism in MYC-driven neuroblastoma.
  • JMJD6 controls alternative splicing of kidney-type glutaminase (KGA) and glutaminase C (GAC) isoforms.
  • JMJD6 is linked to the anti-cancer effects of indisulam, a drug targeting RBM39.

Conclusions:

  • JMJD6 promotes a cancer-associated metabolic program linked to alternative pre-mRNA splicing.
  • Targeting JMJD6 presents a potential therapeutic strategy for MYC-driven cancers, including neuroblastoma.
Keywords:
GLSJMJD6cancer biologyindisulamneuroblastomanonesplicing

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