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Open Access Research article

Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene

Umasuthan Srirangalingam1, Scott A Akker1, Dennis Norman12, Naveenan Navaratnam3, Shern L Chew1 and Bernard Khoo14*

Author Affiliations

1 Department of Endocrinology, William Harvey Research Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK

2 Current address: Argenta Discovery Ltd, 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, UK

3 RNA Editing Group, MRC Clinical Sciences Centre, Division of Clinical Sciences, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

4 Current address: Department of Endocrinology, UCL Medical School, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK

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BMC Molecular Biology 2013, 14:5  doi:10.1186/1471-2199-14-5

Published: 7 February 2013

Abstract

Background

Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus.

Results

We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon.

Conclusion

Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB.

Keywords:
Apolipoprotein B; RNA splicing; Splicing regulation; Splice sites; Splicing silencers