Heterogeneous nuclear ribonucleoprotein F/H proteins modulate the alternative splicing of the apoptotic mediator

Related Experiment Video

Updated: Aug 18, 2026

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

Daniel Garneau1, Timothée Revil, Jean-François Fisette

  • 1RNA/RNP Group, Département de microbiologie et d'infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Québec, Canada.

The Journal of Biological Chemistry
|April 20, 2005
PubMed

Insights

Researchers identified key elements controlling Bcl-x alternative splicing, favoring the pro-apoptotic Bcl-x(S) variant. Heterogeneous nuclear ribonucleoprotein (hnRNP) F and H proteins bind to a G-rich element, promoting Bcl-x(S) production and regulating apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Bcl-x, a Bcl-2 family protein, regulates apoptosis.
  • Alternative splicing of Bcl-x pre-mRNA produces Bcl-x(S) (pro-apoptotic) and Bcl-x(L) (anti-apoptotic) isoforms.

Purpose of the Study:

  • Investigate elements and factors governing Bcl-x alternative splicing.
  • Determine the role of specific RNA-binding proteins in isoform production.

Main Methods:

  • Deletion mutagenesis of a human Bcl-x minigene in HeLa cells.
  • In vitro splicing assays with recombinant hnRNP F and H proteins.
  • RNA interference targeting hnRNP F and H.

Main Results:

  • Two regulatory regions (B3 and B2) in exon 2 of Bcl-x pre-mRNA identified.
  • A G-rich element (B2G) within the B2 region promotes Bcl-x(S) production.
  • hnRNP F and H proteins bind to B2G and enhance Bcl-x(S) splicing.
  • Knockdown of hnRNP F/H reduces the Bcl-x(S)/Bcl-x(L) ratio.

Conclusions:

  • hnRNP F/H proteins play a positive role in promoting the pro-apoptotic Bcl-x(S) isoform.
  • Identified a novel mechanism of alternative splicing regulation involving hnRNP F/H and G-rich elements.
  • Provides insights into the regulation of apoptosis by Bcl-x splicing.

More Related Videos

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Examining BCL-2 Family Function with Large Unilamellar Vesicles08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...