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Related Concept Videos

Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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...
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...
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...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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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...

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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Histone deacetylase activity modulates alternative splicing.

Jarmila Hnilicová1, Samira Hozeifi, Eva Dušková

  • 1Department of RNA Biology, Institute of Molecular Genetics AS CR, Prague, Czech Republic.

Plos One
|February 12, 2011
PubMed
Summary
This summary is machine-generated.

Histone deacetylase (HDAC) activity impacts RNA splicing by altering chromatin structure and protein interactions. HDAC inhibition affects gene splicing, demonstrating a link between chromatin modifications and gene expression regulation.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Splicing decisions are increasingly understood to occur during nascent RNA synthesis while associated with chromatin.
  • Histone deacetylases (HDACs) are key epigenetic regulators influencing chromatin structure.

Purpose of the Study:

  • To investigate the role of histone deacetylase (HDAC) activity in regulating alternative splicing.
  • To elucidate the molecular mechanisms by which HDACs influence splice site selection.

Main Methods:

  • Utilized splicing-sensitive microarrays to identify genes with altered splicing upon HDAC inhibition.
  • Measured histone H4 acetylation and RNA Polymerase II (Pol II) processivity.
  • Assessed co-transcriptional association of splicing regulator SRp40 using chromatin immunoprecipitation.
  • Employed gene depletion and rescue experiments using HDAC1 and a catalytically inactive mutant.

Main Results:

  • HDAC inhibition altered splicing in approximately 700 genes.
  • HDAC inhibition led to increased histone H4 acetylation and enhanced Pol II processivity.
  • Reduced co-transcriptional binding of SRp40 to the fibronectin exon was observed after HDAC inhibition.
  • Depletion of HDAC1 mimicked global HDAC inhibition effects on fibronectin splicing, which were reversed by wild-type HDAC1 expression.

Conclusions:

  • HDAC activity plays a significant role in modulating alternative splicing decisions.
  • Chromatin modifications, influenced by HDACs, directly impact splice site selection.
  • These findings provide molecular insights into the interplay between HDACs, chromatin, and RNA splicing.