3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons
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...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/617842 |
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| author | Sunghee Cho Heegyum Moon Tiing Jen Loh Hyun Kyung Oh Hey-Ran Kim Myung-Geun Shin D. Joshua Liao Jianhua Zhou Xuexiu Zheng Haihong Shen |
| author_facet | Sunghee Cho Heegyum Moon Tiing Jen Loh Hyun Kyung Oh Hey-Ran Kim Myung-Geun Shin D. Joshua Liao Jianhua Zhou Xuexiu Zheng Haihong Shen |
| author_sort | Sunghee Cho |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5569434416a9446aafce03d7631d558f |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-5569434416a9446aafce03d7631d558f2025-02-03T06:47:54ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/6178426178423′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby ExonsSunghee Cho0Heegyum Moon1Tiing Jen Loh2Hyun Kyung Oh3Hey-Ran Kim4Myung-Geun Shin5D. Joshua Liao6Jianhua Zhou7Xuexiu Zheng8Haihong Shen9School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaDepartment of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of KoreaDepartment of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun 519-763, Republic of KoreaThe Hormel Institute, University of Minnesota, Austin, MN 55912, USAJiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, ChinaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of KoreaSpinal 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.http://dx.doi.org/10.1155/2014/617842 |
| spellingShingle | Sunghee Cho Heegyum Moon Tiing Jen Loh Hyun Kyung Oh Hey-Ran Kim Myung-Geun Shin D. Joshua Liao Jianhua Zhou Xuexiu Zheng Haihong Shen 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons The Scientific World Journal |
| title | 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons |
| title_full | 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons |
| title_fullStr | 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons |
| title_full_unstemmed | 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons |
| title_short | 3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons |
| title_sort | 3 splice site sequences of spinal muscular atrophy related smn2 pre mrna include enhancers for nearby exons |
| url | http://dx.doi.org/10.1155/2014/617842 |
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