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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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Alternative RNA Splicing02:18

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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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What is Gene Expression?01:36

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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...
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Chromatin Structure Regulates pre-mRNA Processing02:41

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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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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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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...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Expression and splicing mediate distinct biological signals.

Søren Helweg Dam1, Lars Rønn Olsen1, Kristoffer Vitting-Seerup2

  • 1Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.

BMC Biology
|October 19, 2023
PubMed
Summary

Alternative splicing significantly impacts gene expression, contributing nearly half of the biological signal in RNA sequencing studies. Understanding isoform-level changes is crucial for uncovering biological insights missed by gene-centric approaches.

Keywords:
Alternative splicingBioinformaticsGene expressionGene regulationIsoformIsoform expressionRNA-seqRNA-sequencingSystems biology

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Alternative splicing generates diverse gene isoforms crucial for cellular functions, development, and disease.
  • The full extent and biological significance of alternative splicing remain largely unexplored.
  • Current RNA sequencing analyses may overlook critical isoform-specific information.

Purpose of the Study:

  • To quantify the contribution of alternative splicing to biological signals in gene expression data.
  • To assess the distinct and shared biological information conveyed by gene expression and splicing.

Main Methods:

  • Development and application of paired Gene Set Enrichment Analysis (GSEA).
  • Profiling of transcriptional changes across 100 diverse RNA sequencing datasets.
  • Systematic analysis of isoform-level expression and splicing patterns.

Main Results:

  • Alternative splicing changes account for an average of 48.1% of the biological signal in expression analyses.
  • Gene-set enrichment analysis revealed both shared and distinct biological signals between expression and splicing.
  • Demonstrated the significant role of splicing in cellular and disease processes.

Conclusions:

  • Alternative splicing is a major regulator of biological processes and the human condition.
  • Many current RNA sequencing studies may be missing key biological insights due to a gene-centric focus.
  • Advocates for a shift towards an isoform-centric research paradigm for a comprehensive understanding of biological systems.