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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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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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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.
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...
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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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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
Master Transcription Regulators02:23

Master Transcription Regulators

6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Combinatorial Gene Control02:33

Combinatorial Gene Control

8.3K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Related Experiment Video

Updated: Jun 15, 2025

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

12.9K

KDM3A and KDM3B regulate alternative splicing in mouse pluripotent stem cells.

Caleb M Dillingham1,2,3, Harshini Cormaty1,2,4, Ellen C Morgan1,2

  • 1Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.

Iscience
|June 13, 2025
PubMed
Summary

Histone demethylases KDM3A and KDM3B regulate mouse stem cell identity through RNA splicing, not just histone modification. This reveals a new role in post-transcriptional gene regulation.

Keywords:
Model organismMolecular mechanism of gene regulationProteomicsStem cells researchTranscriptomics

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Related Experiment Videos

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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Area of Science:

  • Cell Biology
  • Epigenetics
  • Molecular Biology

Background:

  • Histone modifying enzymes maintain cell identity by regulating chromatin.
  • Mouse embryonic stem cells (mESCs) have low gene repression for rapid differentiation.
  • KDM3 family demethylases remove repressive H3K9me2 marks.

Purpose of the Study:

  • To investigate the role of KDM3 proteins in mouse pluripotent embryonic stem cells (mESCs).
  • To explore potential non-histone modification functions of KDM3A and KDM3B.
  • To understand the impact of KDM3 proteins on RNA processing and cell identity.

Main Methods:

  • Proteomic analysis to identify KDM3 interacting partners.
  • Acute degradation of endogenous KDM3A and KDM3B proteins.
  • Analysis of splicing patterns and histone modification status (H3K9me2).

Main Results:

  • KDM3A and KDM3B interact with RNA processing factors (EFTUD2, PRMT5).
  • Protein degradation alters splicing independently of H3K9me2 or catalytic activity.
  • Splicing changes mimic ground state pluripotency and affect key genes (Dnmt3b, Tcf12).

Conclusions:

  • KDM3 proteins have a non-canonical role in post-transcriptional regulation.
  • Histone demethylases can influence cell identity through alternative splicing.
  • These findings expand the known functions of KDM3 family enzymes.