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A Splicing Reporter Tuned to Non-AG Acceptor Sites Reveals that Luteolin Enhances the Recognition of Non-canonical Acceptor Sites

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/64435

Title: A Splicing Reporter Tuned to Non-AG Acceptor Sites Reveals that Luteolin Enhances the Recognition of Non-canonical Acceptor Sites
Authors: Chiba, Masanori Browse this author
Ariga, Hiroyoshi Browse this author →KAKEN DB
Maita, Hiroshi Browse this author →KAKEN DB
Keywords: 3 ' splice site
fidelity
luteolin
pre-mRNA splicing
reporter assay
Issue Date: Feb-2016
Publisher: Wiley-Blackwell
Journal Title: Chemical biology & drug design
Volume: 87
Issue: 2
Start Page: 275
End Page: 282
Publisher DOI: 10.1111/cbdd.12656
PMID: 26348996
Abstract: Removal of an intron requires precise recognition of the splice donor and acceptor sites located at the 50 and 30 termini of introns. Although the roles of these sequences differ, mutations in both sites easily block normal splicing and produce an aberrant mRNA. For example, many splice-site mutations occur in patients with inherited diseases. Several approaches have been evaluated to restore expression of a functional protein; however, because of the strict requirement for an AG dinucleotide at the 30 terminus of a U2-type intron, no method is available to correct splicing at a mutated sequence. To identify compounds that allow splicing at the non-AG acceptor site, in the present study we constructed a reporter gene with a modified polypyrimidine tract. However, the modified polypyrimidine tract mediated splicing at adjacent non-canonical acceptor sites, including the original mutated site. Further, we show that certain flavones such as luteolin and apigenin enhanced aberrant splicing at the non-canonical acceptor site of the reporter gene. These results suggest that the reporter gene and luteolin may be useful for further screening to identify molecules that correct aberrant splicing caused by a disease-associated splice acceptor site mutation.
Rights: This is the peer reviewed version of the following article: Chiba, M., Ariga, H. and Maita, H. (2016), A Splicing Reporter Tuned to Non-AG Acceptor Sites Reveals that Luteolin Enhances the Recognition of Non-canonical Acceptor Sites. Chemical Biology & Drug Design, 87: 275-282., which has been published in final form at http://dx.doi.org/10.1111/cbdd.12656. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: article (author version)
URI: http://hdl.handle.net/2115/64435
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 米田 宏

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