title: 3' Splice site sequences of spinal muscular atrophy related SMN2 pre-mRNA include enhancers for nearby exons.
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.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Sunghee
authors.identifier: 0000-0003-0700-6213
authors.initials: S
authors.lastname: Cho
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Heegyum
authors.identifier: 0000-0003-0152-5506
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Hyun Kyung
authors.identifier: 0000-0003-0364-9502
authors.initials: HK
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of Korea.
authors.forename: Hey-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of Korea.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Liao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Jianhua
authors.identifier: 0000-0001-8946-3121
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005091:Exons; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D012322:RNA Precursors; D022821:RNA Splice Sites; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics*
chemical_list: D012322:RNA Precursors; D022821:RNA Splice Sites; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein