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Related Concept Videos

RNA Splicing01:32

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...
RNA Splicing01:32

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...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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...
Pre-mRNA Processing: RNA Splicing01:32

Pre-mRNA Processing: 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...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

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Updated: Jul 10, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

A combinatorial code for splicing silencing: UAGG and GGGG motifs.

Kyoungha Han1, Gene Yeo, Ping An

  • 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Plos Biology
|April 15, 2005
PubMed
Summary

Researchers identified a specific RNA sequence pattern (UAGG and GGGG motifs) that silences a brain-specific exon in gene expression. This discovery reveals a new layer of combinatorial control in alternative splicing, impacting tissue-specific mRNA production.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Neuroscience

Background:

  • Alternative pre-mRNA splicing regulates gene expression through tissue-specific mRNA isoforms.
  • Combinatorial control of splicing remains poorly understood, despite the known roles of regulatory sequences.

Purpose of the Study:

  • To identify the molecular mechanisms underlying combinatorial control of alternative splicing.
  • To investigate the role of specific RNA motifs in regulating the CI cassette exon of the glutamate NMDA R1 receptor (GRIN1) transcript.

Main Methods:

  • Molecular approaches to identify RNA motifs and their interactions.
  • Functional studies using reporter assays to test splicing regulation.
  • Genome-wide computational analysis and RT-PCR to identify conserved regulatory patterns.

Main Results:

  • A ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs was identified as a cooperative silencer of the GRIN1 CI cassette exon.
  • Disruption or de novo introduction of these motifs altered exon splicing, converting constitutive exons to skipped or vice versa.
  • hnRNP A1 mediated silencing, while hnRNP H antagonized it.
  • A conserved motif pattern was identified in skipped human and mouse exons, suggesting broader biological relevance.

Conclusions:

  • The identified multi-component silencing code plays a significant role in tissue-specific regulation of the CI cassette exon.
  • This regulatory mechanism may represent a general molecular language for intricate splicing pattern coordination across genes.