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Related Concept Videos

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.
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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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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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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...
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Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
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Differential splicing using whole-transcript microarrays.

Mark D Robinson1, Terence P Speed

  • 1Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia. mrobinson@wehi.edu.au

BMC Bioinformatics
|May 26, 2009
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Summary
This summary is machine-generated.

We developed FIRMAGene to detect differential splicing events using Affymetrix Gene 1.0 ST arrays. This method identifies tissue-specific alternative splicing by analyzing probe-level data, complementing differential expression analysis.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Affymetrix microarrays enable genome-wide alternative splicing studies.
  • The Gene 1.0 ST array interrogates full-length transcripts, offering potential for splicing analysis.
  • Exploring the Gene 1.0 ST platform for differential splicing detection.

Purpose of the Study:

  • To develop and validate a novel method for identifying differential splicing events.
  • To leverage the Gene 1.0 ST microarray platform for alternative splicing discovery.
  • To complement existing differential expression analyses with splicing insights.

Main Methods:

  • Utilizing the Robust Multichip Analysis (RMA) statistical model to partition probe-level data.
  • Developing a statistic to identify adjacent poorly fitting probes as indicators of differential splicing.
  • Applying the FIRMAGene approach to analyze a public tissue panel dataset.

Main Results:

  • Demonstrated tissue-specific alternative splicing events using the Gene 1.0 ST platform.
  • Showed strong correspondence between Gene 1.0 ST and Exon 1.0 ST platforms for alternative splicing evidence.
  • Identified numerous examples of differential splicing in the analyzed dataset.

Conclusions:

  • Introduced FIRMAGene, a new computational approach for detecting differentially spliced genes.
  • Validated FIRMAGene with known splicing examples and discussed data interpretation challenges.
  • Provided freely available R package for FIRMAGene implementation.