J Cancer 2011; 2:386-400. doi:10.7150/jca.2.386

Research Paper

Complex Alternative Splicing of the Smarca2 Gene Suggests the Importance of Smarca2-B Variants

Min Yang1*, Yuan Sun1, Ling Ma2, Chenguang Wang3, Jian-min Wu2, Anding Bi1, D. Joshua Liao1 ✉

1. Hormel Institute, The University of Minnesota, Austin, MN 55912, USA
2. Guangxi Veterinary Research Institute, Nanning, Guangxi 530001, P.R. China
3. Department of Stem Cell and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA
*Current address: School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan 610083, P.R. China

Abstract

BRM is an ATPase component of the SWI/SNF complex that regulates chromatin remodeling and cell proliferation and is considered a tumor suppressor. In this study we characterized transcripts from the Smarca2 gene that encodes the BRM protein. We found that the human Smarca2 gene (hSmarca2), like its mouse counterpart (mSmarca2), also initiated a short transcript from intron 27 of the long transcript. We name the long and short transcripts as Smarca2-a and Smarca2-b, respectively. Like its human counterpart, mSmarca2-a also underwent alternative splicing at the 54-bp exon 29. The hSmarca2-b had two alternative initiation sites and underwent alternative splicing at three different 3' sites of exon 1 and at exons 2, 3 and/or 5. We identified nine hSmarca2-b mRNA variants that might produce five different proteins. mSmarca2-b also underwent alternative splicing at exon 3 and/or exon 5, besides alternatively retaining part of intron 1 in exon 1. Smarca2-b was expressed more abundantly than Smarca2-a in many cell lines and was more sensitive to serum starvation. Moreover, cyclin D1 also regulated the expression of both Smarca2-a and Smarca2-b in a complex manner. These data suggest that the functions of the Smarca2 gene may be very complex, not just simply inhibiting cell proliferation, and in certain situations may be elicited mainly by expressing the much less known Smarca2-b, not the better studied Smarca2-a and its products BRM proteins.

Keywords: Alternative splicing, Tumor suppressor gene, BRM, Smarca2, SWI/SNF complex, Cancer, Cyclin D1

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How to cite this article:
Yang M, Sun Y, Ma L, Wang C, Wu Jm, Bi A, Liao DJ. Complex Alternative Splicing of the Smarca2 Gene Suggests the Importance of Smarca2-B Variants. J Cancer 2011; 2:386-400. doi:10.7150/jca.2.386. Available from http://www.jcancer.org/v02p0386.htm