An RNA architectural locus control region involved in Dscam mutually exclusive splicing

Xuebin Wang, Guoli Li, Yun Yang, Wenfeng Wang, Wenjing Zhang, Huawei Pan, Peng Zhang, Yuan Yue, Hao Lin, Baoping Liu, Jingpei Bi, Feng Shi, Jinping Mao, Yijun Meng, Leilei Zhan and Yongfeng Jin ()
Additional contact information
Xuebin Wang: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Guoli Li: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Yun Yang: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Wenfeng Wang: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Wenjing Zhang: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Huawei Pan: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Peng Zhang: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Yuan Yue: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Hao Lin: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Baoping Liu: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Jingpei Bi: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Feng Shi: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Jinping Mao: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Yijun Meng: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Leilei Zhan: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)
Yongfeng Jin: Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus)

Nature Communications, 2012, vol. 3, issue 1, 1-11

Abstract: Abstract The most striking example of alternative splicing in a Drosophila melanogaster gene is observed in the Down syndrome cell adhesion molecule, which can generate 38,016 different isoforms. RNA secondary structures are thought to direct the mutually exclusive splicing of Down syndrome cell adhesion molecule, but the underlying mechanisms are poorly understood. Here we describe a locus control region that can activate the exon 6 cluster and specifically allow for the selection of only one exon variant in combination with docking site selector sequence interactions. Combining comparative genomic studies of 63 species with mutational analysis reveals that intricate, tandem multi-‘subunit’ RNA structures within the locus control region activate species-appropriate alternative variants. Importantly, strengthening the weak splice sites of the target exon can remove the locus control region dependence. Our findings not only provide a locus control region-dependent mechanism for mutually exclusive splicing, but also suggest a model for the evolution of increased complexity in a long-range RNA molecular machine.

Date: 2012
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DOI: 10.1038/ncomms2269

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