PROCESSING OF HUMAN APOLIPOPROTEIN-B MRNA

人载脂蛋白-B mRNA 的加工

• 批准号: 3363791
• 负责人: SUSAN M BERGET
• 金额: $ 14.63万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3363791
• 关键词: RNA splicing; apolipoproteins; gene mutation; genetic regulatory element; human genetic material tag; messenger RNA; polyadenylate; tissue /cell culture

Most vertebrate genes are split into multiple exons and introns; introns are large; exons, in contrast, are very small. The average size of a vertebrate internal exon is 137 nucleotides; very few exceed 300 nucleotides. Occasionally, large exons exist. This proposal is concerned with investigating if the splicing machinery restricts exon size; if it does, how do large exons by-pass the normal restrictions on size during splicing; and is there a functional advantage to large exons? One naturally occurring large exon is exon 26 of the murine and human apolipoprotein-b gene. This exon is over 7 kb in length. In human liver it is spliced correctly to produce the large apo-bl00 protein of 512 kd involved in the metabolism of endogenous lipids. In human intestine, a mRNA is produced that includes an RNA editing event. Editing produces a translational stop codon within exon 26; translation produces a short apo-b48 protein of 252 kd involved in the metabolism of exogenous lipids. Editing is accompanied by polyadenylation within exon 26. This proposal describes experiments designed to understand how exon 26 is correctly recognized in liver and alternatively recognized in intestine. The regulation of apolipoprotein-b is important to normal lipid metabolism and human heart disease. Understanding the mechanism whereby the two forms of apo-b are generated should increase our knowledge of heart disease and how to combat it.

大多数脊椎动物基因被分成多个外显子和内含子； 内含子大；相比之下，外显子非常小。 平均尺寸 脊椎动物内外显子的长度为137个核苷酸；很少有超过300的 核苷酸。 有时，存在大的外显子。 这个提议是 涉及调查剪接机器是否限制外显子 尺寸;如果是的话，大外显子如何绕过正常的限制 拼接时的尺寸；大外显子有功能优势吗？ 一种天然存在的大外显子是小鼠的外显子 26， 人类载脂蛋白-b 基因。 该外显子长度超过 7 kb。 在人类 肝脏被正确剪接以产生大的 apo-bl00 蛋白 512 kd 参与内源性脂质的代谢。 在人类 在肠道中，产生了包含 RNA 编辑事件的 mRNA。 编辑在外显子 26 内产生翻译终止密码子；翻译 产生 252 kd 的短 apo-b48 蛋白，参与代谢 外源性脂质。 编辑伴随着外显子内的聚腺苷酸化 26. 该提案描述了旨在了解外显子如何 26 在肝脏中被正确识别，并且在 肠。 载脂蛋白-b 的调节对于正常情况很重要 脂质代谢与人类心脏病。 了解机制 由此产生两种形式的 apo-b 应该会增加我们的 了解心脏病以及如何对抗心脏病。