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The Scientific World Journal
Volume 2014, Article ID 617842, 9 pages
http://dx.doi.org/10.1155/2014/617842
Research Article

3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons

1School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea
2Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of Korea
3The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
4Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China

Received 24 November 2013; Accepted 19 December 2013; Published 27 January 2014

Academic Editors: B. Bardoni and E. J. Benz

Copyright © 2014 Sunghee Cho et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Spinal muscular atrophy (SMA) is a human genetic disease which occurs because of the deletion or mutation of SMN1 gene. SMN1 gene encodes the SMN protein which plays a key role in spliceosome assembly. Although human patients contain SMN2, a duplicate of SMN1, splicing of SMN2 produces predominantly exon 7 skipped isoform. In order to understand the functions of splice site sequences on exon 7 and 8, we analyzed the effects of conserved splice site sequences on exon 7 skipping of SMN2 and SMN1 pre-mRNA. We show here that conserved 5′ splice site sequence of exon 7 promoted splicing of nearby exons and subsequently reduced splicing of distant exons. However, to our surprise, conserved 3′ splice site sequence of exon 7 and 8 did not promote splicing of nearby exons. By contrast, the mutation inhibited splicing of nearby exons and subsequently promoted splicing of distant exons. Our study shows that 3′ splice sites of exon 7 and 8 contain enhancer for their splice site selection, in addition to providing cleavage sites.