Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/104198
Title: Identification of cis-acting elements and splicing factors involved in the regulation of BIM pre-mRNA splicing
Authors: Juan, Wen Chun
Roca, Xavier
Ong, S. Tiong
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2014
Source: Juan, W. C., Roca, X., & Ong, S. T. (2014). Identification of cis-Acting Elements and Splicing Factors Involved in the Regulation of BIM Pre-mRNA Splicing. PLoS ONE, 9(4), e95210-.
Series/Report no.: PLoS ONE
Abstract: Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and splicing factors involved in BIM alternative splicing, as a step to better understand the regulation of BIM expression. We analyzed a recently discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We found that this region harbors multiple redundant cis-acting elements that repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing silencer at the 3′ end of the deletion that is important for excluding exon 3. We also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these findings start building our understanding of the cis-acting elements and splicing factors that regulate BIM alternative splicing, and also suggest potential approaches to alter BIM splicing for therapeutic purposes.
URI: https://hdl.handle.net/10356/104198
http://hdl.handle.net/10220/19565
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0095210
Rights: © 2014 Juan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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