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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...
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...
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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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Alternative RNA splicing complexes containing the scaffold attachment factor SAFB2.

Kate A Sergeant1, Cyril F Bourgeois, Caroline Dalgliesh

  • 1Institute of Human Genetics, University of Newcastle, International Centre for Life, Central Parkway, Newcastle, NE1 3BZ, UK.

Journal of Cell Science
|January 4, 2007
PubMed
Summary

Scaffold attachment factor SAFB2 forms larger nuclear complexes than SAFB1 and both regulate pre-mRNA splicing. These proteins may act as pre-assembled modules for alternative splicing regulation.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Scaffold attachment factors (SAFB1 and SAFB2) are implicated in linking pre-mRNA splicing, intracellular signaling, and transcription.
  • Understanding the distinct roles and interactions of SAFB1 and SAFB2 is crucial for elucidating their functions in gene regulation.

Purpose of the Study:

  • To investigate the distinct nuclear localization, complex formation, and expression patterns of SAFB1 and SAFB2.
  • To determine the role of SAFB proteins in pre-mRNA splicing, particularly alternative splicing.
  • To explore the interactions of SAFB proteins with other splicing regulators.

Main Methods:

  • Utilized novel mono-specific antisera to detect endogenous SAFB1 and SAFB2 proteins.
  • Analyzed protein distribution within the nucleus and determined complex sizes using techniques like size-exclusion chromatography.
  • Assessed protein expression patterns in adult human testis.
  • Investigated the regulatory role of SAFB proteins in alternative splicing, specifically focusing on a tra2beta variable exon.
  • Examined interactions between SAFB proteins and other splicing factors, including SR proteins and related regulators.

Main Results:

  • Endogenous SAFB2 protein exhibits a different nuclear spatial distribution and forms significantly larger nuclear complexes (up to 670 kDa) compared to SAFB1, which exists as smaller complexes or monomers.
  • SAFB2 shows a distinct expression pattern in adult human testis.
  • Both SAFB1 and SAFB2 function as negative regulators of a tra2beta variable exon, indicating their involvement in alternative splicing.
  • Stable complexes containing SAFB1, SAFB2, Sam68, and hnRNPG were identified, existing independently of free SAFB1.
  • No stable interactions were detected between SAFB proteins and SR or SR-related splicing regulators, despite their presence in large complexes.
  • Alternative splicing regulator complexes appear to exist independently of nucleic acids, suggesting pre-assembly or storage mechanisms.

Conclusions:

  • SAFB2 forms larger nuclear complexes than SAFB1, with distinct localization and expression, suggesting specialized roles.
  • SAFB proteins are involved in the negative regulation of alternative splicing.
  • The findings suggest that SAFB proteins, along with Sam68 and hnRNPG, form stable complexes that may function as pre-assembled modules or storage compartments for alternative splicing regulation.