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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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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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Chromatin Structure and RNA Splicing02:41

Chromatin Structure and RNA Splicing

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Pre-mRNA Processing: RNA Splicing01:36

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Transcription Elongation Factors

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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
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Related Experiment Videos

Chromatin-bound U2AF2 splicing factor ensures exon inclusion.

Weifang Wu1, Kami Ahmad1, Steven Henikoff2

  • 1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Molecular Cell
|May 2, 2025
PubMed
Summary

Splicing factors like U2AF2 bind near active promoters and within gene bodies, enhancing exon selection accuracy. This chromatin-bound U2AF2 helps regulate efficient co-transcriptional mRNA splicing.

Keywords:
H3K36me3RNA polymerase IISF3B155U2AF35U2AF65co-transcriptional RNA splicingexon definition

Related Experiment Videos

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • Co-transcriptional mRNA splicing is crucial for gene expression.
  • Mechanisms by which splicing factors ensure accurate exon selection remain incompletely understood.

Purpose of the Study:

  • To investigate the binding patterns and regulatory roles of splicing factors SF3B1, U2AF1, and U2AF2 during co-transcriptional splicing.
  • To elucidate the function of U2AF2 in enhancing exon selection accuracy and its dependence on chromatin modifications.

Main Methods:

  • CUT&RUN profiling in K562 cells to map protein-DNA interactions.
  • RNase A treatment to assess transcript dependence of factor binding.
  • Analysis of U2AF2 binding in relation to histone modifications (H3K36me3) and gene expression levels.

Main Results:

  • SF3B1, U2AF1, and U2AF2 bind near active gene promoters, interacting with nascent transcripts.
  • U2AF2 accumulates in intron-containing gene bodies and requires H3K36me3 for binding.
  • Chromatin-bound U2AF2 preferentially binds exons of highly expressed genes, improving splicing accuracy, particularly for skipped exons.

Conclusions:

  • U2AF2 plays a critical role in enhancing exon selection accuracy during co-transcriptional splicing.
  • Chromatin-bound U2AF2, regulated by H3K36me3, contributes to the homeostatic control of splicing efficiency.
  • These findings provide a mechanistic link between chromatin state and splicing factor function.