| Project/Area Number |
17390102
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
INOUE Ken National Center of Neurology and Psychiatry, National Institution of Neuroscience,Dept of Mental Retardation Birth Defect Research., Division Head (30392418)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Kyoko National Institution of Neuroscience., Visiting Fellow (70392420)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,960,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2007: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Nonsence-mediate decay / Alu / genome / RNA intereference / evolution / alternative splicing |
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| Research Abstract |
Although thousands of intronic Alu elements, the most abundant interspersed elements in human genome, have predicted capability to become alternative exons, only a small number of genes actually incorporate Alu elements as expressed splicing variants by unknown genomic basis. Here we tested our hypothesis that nonsense-mediated mRNA decay (NMD), an mRNA surveillance system by which mRNAs containing premature termination codons (PTCs) are selectively detected and disrupted, can serve as post-transcriptional eliminator of Alu-containing splicing variants (ASVs). Examination of the expression level of ASVs in 21 human genes revealed that ASVs are generally present as minor alleles in multiple human tissues as well as in HeLa and SH-SY5Y cells. Removal of NMD in these cells resulted in an upregulation of ASVs in some genes, suggesting a partial role of NMD in suppressing the expression of ASVs Furthermore, a serial introduction of PTCs in the ADARB1 gene, of which ASV is expressed as a major allele, failed to trigger NMD. To delineate whether this insensitivity to NMD is modulated by low expression of ASVs, The expression of ASVs is affected by the change of splicing efficiency, which caused by substitutions of nucleotide, rather than by NMD. The strength of donor splice sites in ASVs was weaker than in constitutive and alternative exons and the number of ESEs in ASVs were smaller than in constitutive and alternative exons. These results suggested that the majority of ASVs containing PTCs are produced at low level in native status and are only partially sensitive to NMD.
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