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Related Concept Videos

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...
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...
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Master Transcription Regulators02:23

Master 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...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...

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

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Published on: October 9, 2014

Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and

Twishasri Dasgupta1, Samantha J Stillwagon, Andrea N Ladd

  • 1Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Plos One
|February 26, 2013
PubMed
Summary

CUG-BP, Elav-like family (CELF) proteins regulate heart splicing. Inhibiting CELF in mice caused dilated cardiomyopathy by altering SRF activity and contractile gene expression.

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Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Genetics

Background:

  • The CUG-BP, Elav-like family (CELF) of proteins are crucial regulators of alternative splicing, particularly within the heart.
  • Dysregulation of CELF activity can lead to cardiac dysfunction, as observed in certain genetic models.

Purpose of the Study:

  • To investigate the molecular mechanisms by which CELF proteins influence cardiac function and gene expression.
  • To explore the relationship between CELF-mediated alternative splicing and the activity of the serum response factor (SRF) network in the heart.

Main Methods:

  • Gene expression profiling using microarrays in wild-type and MHC-CELFΔ transgenic mice with varying levels of CELF inhibition.
  • Gene ontology and pathway analyses to identify affected biological processes.
  • Network analysis to assess the impact on the SRF network and its downstream targets.

Main Results:

  • Dilated cardiomyopathy, characterized by splicing defects and contractile dysfunction, was observed in MHC-CELFΔ mice.
  • Contraction and calcium signaling pathways were significantly affected, with altered SRF network activity.
  • Downstream SRF targets were upregulated in MHC-CELFΔ mice, while SRF inhibitors were downregulated, suggesting increased SRF activity.

Conclusions:

  • CELF-mediated alternative splicing plays a significant role in regulating cardiac contractile gene expression.
  • Modulation of SRF activity by CELF proteins is a key mechanism in maintaining normal cardiac function.
  • These findings highlight a direct link between splicing regulation and cardiac transcription factor activity in heart failure pathogenesis.