Determining the Impact of Alternative Splicing Events on Transcriptome Dynamics

Overview

Journal BMC Res Notes

Publisher Biomed Central

Specialties Biology
General Medicine

Date 2008 Oct 28

PMID 18950505

Citations 7

Authors

Emmanuelle Wilhelm

Francois-Xavier Pellay

Arndt Benecke

Brendan Bell

Affiliations

Soon will be listed here.

Abstract

Background: The complete sequencing of the human genome and its subsequent analysis revealed a predominant role for alternative splicing in the generation of proteome diversity. Splice switching oligonucleotides (SSOs) are a powerful and specific tool to experimentally control alternative splicing of endogenous messenger RNAs in living cells. SSOs also have therapeutic potential to treat diseases that are caused by aberrant splicing. The assignment of biological roles to alternative splicing events of currently unknown function promises to provide a largely untapped source of potential new therapeutic targets. Here we have developed a protocol that combines high sensitivity microarrays with the transfection of SSOs to monitor global changes in gene expression downstream of alternate, endogenous splice events.

Results: When applied to a well-characterized splicing event in the Bcl-x gene, the application of high sensitivity microarrays revealed a link between the induction of the Bcl-xS isoform and the repression of genes involved in protein synthesis.

Conclusion: The strategy introduced herein provides a useful approach to define the biological impact of any given alternative splicing event on global gene expression patterns. Furthermore, our data provide the first link between Bcl-xS expression and the repression of ribosomal protein gene expression.

Citing Articles

Viral modulation of cellular RNA alternative splicing: A new key player in virus-host interactions?.

Boudreault S, Roy P, Lemay G, Bisaillon M Wiley Interdiscip Rev RNA. 2019; 10(5):e1543.

PMID: 31034770 PMC: 6767064. DOI: 10.1002/wrna.1543.

BIM and NOXA are mitochondrial effectors of TAF6δ-driven apoptosis.

Delannoy A, Wilhelm E, Eilebrecht S, Alvarado-Cuevas E, Benecke A, Bell B Cell Death Dis. 2018; 9(2):70.

PMID: 29358700 PMC: 5833734. DOI: 10.1038/s41419-017-0115-3.

The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis.

Marayati B, Hoskins V, Boger R, Tucker J, Fishman E, Bray A RNA. 2016; 22(9):1349-59.

PMID: 27365210 PMC: 4986891. DOI: 10.1261/rna.055608.115.

Alternative splicing of TAF6: downstream transcriptome impacts and upstream RNA splice control elements.

Kamtchueng C, Stebenne M, Delannoy A, Wilhelm E, Leger H, Benecke A PLoS One. 2014; 9(7):e102399.

PMID: 25025302 PMC: 4099370. DOI: 10.1371/journal.pone.0102399.

Attraction basins as gauges of robustness against boundary conditions in biological complex systems.

Demongeot J, Goles E, Morvan M, Noual M, Sene S PLoS One. 2010; 5(8):e11793.

PMID: 20700525 PMC: 2916819. DOI: 10.1371/journal.pone.0011793.

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