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Related Concept Videos

RNA Splicing01:32

RNA Splicing

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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...
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Alternative RNA Splicing02:18

Alternative RNA Splicing

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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.
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Chromatin Structure Regulates pre-mRNA Processing02:41

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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Negative Regulator Molecules01:23

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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General Transcription Factors01:30

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Pre-mRNA Processing: RNA Splicing01:36

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Related Experiment Video

Updated: Jan 11, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
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The splicing factor PTBP1 interacts with RUNX1 and is required for leukemia cell survival.

Arjun Dhir1,2, Alexander Ethell1,2,3, Riley Watkins1,2

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

Leukemia
|November 10, 2025
PubMed
Summary

Runt-related Transcription Factor 1 (RUNX1) interacts with Polypyrimidine Tract Binding Protein 1 (PTBP1) to regulate gene expression and RNA splicing. This interaction is crucial for leukemia cell survival by controlling metabolic gene expression.

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Area of Science:

  • Hematopoiesis and Leukemia Research
  • Molecular Biology and Genomics
  • Cancer Cell Metabolism

Background:

  • Runt-related Transcription Factor 1 (RUNX1) is vital for blood formation and frequently mutated in leukemia.
  • Histone Deacetylase 1 (HDAC1) partners with RUNX1, but its role in transcription suggests non-histone functions.
  • Understanding RUNX1 complex regulation is key to deciphering leukemia pathogenesis.

Purpose of the Study:

  • Identify novel RUNX1 interacting partners in leukemia cells.
  • Decipher the role of these partners in gene regulation and RNA splicing.
  • Investigate the functional impact of RUNX1-partner interactions on leukemia cell metabolism and survival.

Main Methods:

  • Proteomics and genomics to identify RUNX1 interactors.
  • Long-read transcriptomics for gene expression and splicing analysis.
  • Chromatin profiling to map factor occupancy genome-wide.

Main Results:

  • Polypyrimidine Tract Binding Protein 1 (PTBP1) identified as a RUNX1 interactor, dependent on HDAC1.
  • Extensive genome-wide overlap of RUNX1 and PTBP1 binding at active gene promoters.
  • Loss of PTBP1 caused widespread RNA splicing alterations and decreased expression of co-bound metabolic genes.
  • PTBP1 depletion reduced glycolysis, glucose uptake, and induced cell death in AML cells.

Conclusions:

  • The RUNX1-PTBP1 interaction, mediated by HDAC1, is critical for regulating metabolic gene expression in leukemia.
  • This complex controls metabolic pathways essential for leukemia cell proliferation and survival.
  • Targeting the RUNX1-PTBP1 interaction may offer a therapeutic strategy for leukemia.