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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...
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...
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...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Subgroup-specific alternative splicing in medulloblastoma.

Adrian M Dubuc1,2,3, A Sorana Morrissy1,2, Nanne K Kloosterhof4,5

  • 1Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.

Acta Neuropathologica
|February 24, 2012
PubMed
Summary

Medulloblastoma tumors show significantly increased alternative splicing compared to normal brain tissue. These splicing patterns are unique to each molecular subgroup, aiding in classification and revealing potential new biomarkers.

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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Area of Science:

  • Molecular Biology
  • Genomics
  • Oncology

Background:

  • Medulloblastoma is a heterogeneous pediatric brain tumor with four main molecular subgroups: WNT, SHH, Group 3, and Group 4.
  • Understanding transcriptional differences between these subgroups is crucial for diagnosis and treatment.

Purpose of the Study:

  • To investigate alternative splicing patterns across medulloblastoma molecular subgroups.
  • To determine if alternative splicing can serve as a biomarker for medulloblastoma classification.
  • To explore potential regulatory mechanisms of alternative splicing in medulloblastoma.

Main Methods:

  • Analysis of alternative splicing usage in 14 normal cerebellar samples and 103 medulloblastomas.
  • Comparison of splicing patterns between medulloblastoma subgroups.
  • Unsupervised hierarchical clustering of alternative splicing events.
  • Functional annotation of alternatively spliced genes.
  • Correlation analysis with antisense transcript expression.

Main Results:

  • Medulloblastoma samples exhibit a 2.3-fold increase in alternative splicing compared to normal cerebella.
  • Distinct and subgroup-specific alternative splicing patterns were identified.
  • Hierarchical clustering based on splicing accurately assigned tumors to their molecular subgroup.
  • Group 3 and SHH subgroups showed the highest prevalence of subgroup-specific splicing.
  • Alternatively spliced genes were enriched for those involved in neuronal development.
  • Antisense transcripts may play a role in regulating subgroup-specific alternative splicing.

Conclusions:

  • Alternative splicing is a significant source of transcriptional heterogeneity in medulloblastoma.
  • Splicing patterns provide robust markers for medulloblastoma molecular subgroup affiliation.
  • These findings support the distinct biological nature of medulloblastoma subgroups and offer potential new diagnostic markers.