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Expand+Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors

Culler, Stephanie J. and Hoff, Kevin G. and Voelker, Rodger B. and Berglund, J. Andrew and Smolke, Christina D. (2010) Expand+Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors. Nucleic Acids Research, 38 (15). pp. 5152-5165. ISSN 0305-1048. http://resolver.caltech.edu/CaltechAUTHORS:20100920-143401467

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Abstract

Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1093/nar/gkq248 DOIArticle
http://nar.oupjournals.org/content/38/15/5152.abstractPublisherArticle
ORCID:
AuthorORCID
Smolke, Christina D.0000-0002-5449-8495
Additional Information:© The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received November 27, 2009. Revision received March 7, 2010. Accepted March 24, 2010. First published online: April 12, 2010. We thank R. Diamond and D. Perez for FACS assistance and expert technical advice, A. Krainer for the pCISMNx6-wt construct. The Caltech Joseph Jacobs Institute for Molecular Engineering for Medicine (grant to C.D.S.); National Science Foundation (grant MCB-0616264, J.A.B.); National Institutes of Health (fellowship to K.G.H., grant to C.D.S.). Funding for open access charge: National Institutes of Health.
Funders:
Funding AgencyGrant Number
Caltech Joseph Jacobs Institute for Molecular Engineering for Medicine UNSPECIFIED
NSFMCB-0616264
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Record Number:CaltechAUTHORS:20100920-143401467
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20100920-143401467
Usage Policy:This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
ID Code:20052
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Sep 2010 21:45
Last Modified:25 Jul 2017 19:56

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