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Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB

หน่วยงาน Nanyang Technological University, Singapore

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ชื่อเรื่อง : Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB
นักวิจัย : Khoo, Bernard , Roca, Xavier , Chew, Shern L. , Krainer, Adrian R.
คำค้น : DRNTU::Science::Biological sciences::Molecular biology.
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2550
อ้างอิง : Khoo, B., Roca, X., Chew, S. L., & Krainer, A. R. (2007). Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB. BMC Molecular Biology, 8(3). , http://hdl.handle.net/10220/6875 , http://dx.doi.org/10.1186/1471-2199-8-3
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : BMC molecular biology
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Background: Apolipoprotein B (APOB) is an integral part of the LDL, VLDL, IDL, Lp(a) and chylomicron lipoprotein particles. The APOB pre-mRNA consists of 29 constitutively-spliced exons. APOB exists as two natural isoforms: the full-length APOB100 isoform, assembled into LDL, VLDL, IDL and Lp(a) and secreted by the liver in humans; and the C-terminally truncated APOB48, assembled into chylomicrons and secreted by the intestine in humans. Down-regulation of APOB100 is a potential therapy to lower circulating LDL and cholesterol levels. Results: We investigated the ability of 2'O-methyl RNA antisense oligonucleotides (ASOs) to induce the skipping of exon 27 in endogenous APOB mRNA in HepG2 cells. These ASOs are directed towards the 5' and 3' splice-sites of exon 27, the branch-point sequence (BPS) of intron 26–27 and several predicted exonic splicing enhancers within exon 27. ASOs targeting either the 5' or 3' splice-site, in combination with the BPS, are the most effective. The splicing of other alternatively spliced genes are not influenced by these ASOs, suggesting that the effects seen are not due to non-specific changes in alternative splicing. The skip 27 mRNA is translated into a truncated isoform, APOB87SKIP27. Conclusion: The induction of APOB87SKIP27 expression in vivo should lead to decreased LDL and cholesterol levels, by analogy to patients with hypobetalipoproteinemia. As intestinal APOB mRNA editing and APOB48 expression rely on sequences within exon 26, exon 27 skipping should not affect APOB48 expression unlike other methods of down-regulating APOB100 expression which also down-regulate APOB48.

บรรณานุกรม :
Khoo, Bernard , Roca, Xavier , Chew, Shern L. , Krainer, Adrian R. . (2550). Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Khoo, Bernard , Roca, Xavier , Chew, Shern L. , Krainer, Adrian R. . 2550. "Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Khoo, Bernard , Roca, Xavier , Chew, Shern L. , Krainer, Adrian R. . "Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2550. Print.
Khoo, Bernard , Roca, Xavier , Chew, Shern L. , Krainer, Adrian R. . Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2550.