Related Experiment Video
Updated: Jun 23, 2026
10:25
Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
Functional pre- mRNA trans-splicing of coactivator CoAA and corepressor RBM4 during stem/progenitor cell
Yang S Brooks1, Guanghu Wang, Zheqiong Yang
1Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
The Journal of Biological Chemistry
|May 7, 2009
Summary
Alternative splicing of coactivator CoAA and corepressor RBM4 is crucial for stem cell differentiation. Imbalanced splicing, often seen in cancer, disrupts normal development and may lead to disease.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Alternative splicing generates diverse gene products essential for cell differentiation and development.
- Tumor-associated enhancer loss in the coactivator gene CoAA alters its alternative splicing.
- Two intergenic splicing variants, CoAZ and ncCoAZ, were identified between CoAA and RBM4.
Purpose of the Study:
- To investigate the role of alternative and trans-splicing between CoAA and RBM4 during stem/progenitor cell neural differentiation.
- To understand how splice variants of CoAA and RBM4 regulate lineage-specific gene expression and cell fate.
- To explore the evolutionary conservation and regulatory mechanisms of CoAA-RBM4 trans-splicing.
Main Methods:
- Analysis of alternative and trans-splicing patterns during neural differentiation.
- Stable expression of CoAA, RBM4, and their variants in stem/progenitor cells.
- Investigation of the regulatory interaction between CoAA and RBM4 on the Tau gene.
- Phylogenetic analysis of CoAA and RBM4 genes across species.
Main Results:
- Switched alternative and trans-splicing between CoAA and RBM4 transcripts drive lineage-specific differentiation.
- Stable expression of CoAA, RBM4, or their variants disrupts embryoid body formation by preventing this switch.
- CoAA and RBM4 reciprocally regulate Tau gene splicing at exon 10, with splice variants controlling this interaction.
- Mammalian CoAA and RBM4 share ancestry with Drosophila melanogaster Lark, suggesting conserved regulatory roles.
Conclusions:
- Linked splicing control of a transcriptional coactivator (CoAA) and corepressor (RBM4) is integral to stem/progenitor cell differentiation.
- Alternative splicing imbalance of CoAA and RBM4, potentially due to enhancer loss in cancer, can deregulate stem cell differentiation.
- Trans-splicing between CoAA and RBM4 represents an evolutionarily conserved regulatory mechanism critical for development.
More Related Videos
Related Concept Videos
02:18Alternative 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...
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...
02:18Alternative 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...
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...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:23Master Transcription Regulators
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...
02:23Master Transcription Regulators
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...