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Related Concept Videos

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

Chromatin Structure Regulates pre-mRNA Processing

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...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...

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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Novel splice isoforms of STRADalpha differentially affect LKB1 activity, complex assembly and subcellular

P A Marignani1, K D Scott, R Bagnulo

  • 1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Cancer Biology & Therapy
|October 9, 2007
PubMed
Summary

Researchers discovered novel STRADalpha splice isoforms in colorectal cancer cells. These variants impact LKB1 complex formation and AMPK pathway activation, crucial for cell polarity and differentiation.

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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
08:35

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data

Published on: June 24, 2021

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • STRADalpha forms a complex with MO25 and LKB1, a tumor suppressor. LKB1 mutations cause Peutz-Jeghers Syndrome (PJS) and are found in sporadic tumors.
  • The LKB1/STRAD/MO25 complex regulates key signaling pathways in human intestinal epithelial cells, including metabolism, proliferation, and cellular polarity.
  • Cell polarization is essential for enterocyte differentiation, but a full-length STRADalpha transcript was previously unidentified in these cells.

Purpose of the Study:

  • To investigate the expression of endogenous STRADalpha in colorectal cancer cell lines.
  • To identify and characterize novel STRADalpha splice isoforms.
  • To determine how these isoforms affect LKB1 complex assembly, localization, kinase activity, and downstream signaling, particularly the LKB1-dependent AMPK pathway.

Main Methods:

  • Expression analysis of endogenous STRADalpha in five colorectal cancer cell lines with varying differentiation capabilities.
  • Identification of novel STRADalpha splice isoforms.
  • Assessment of the impact of these isoforms on LKB1 complex formation, subcellular localization, and AMPK pathway activation.

Main Results:

  • Discovery of several novel STRADalpha splice isoforms in colorectal cancer cell lines.
  • Demonstration that these isoforms differentially regulate STRADalpha's interaction with LKB1 and MO25.
  • Evidence that STRADalpha isoforms influence the subcellular localization of LKB1 and modulate the activation of the LKB1-dependent AMPK pathway.

Conclusions:

  • Novel STRADalpha splice isoforms are expressed in colorectal cancer cells.
  • These isoforms play a significant role in regulating LKB1 function and downstream signaling pathways involved in cell polarity and differentiation.
  • Understanding these isoforms could provide new insights into colorectal cancer development and potential therapeutic targets.