利用微型基因来鉴定调控可变剪接的因子。

Using mini-genes to identify factors that modulate alternative splicing.

作者信息

Morse Robert, Todd Adrian G, Young Philip J

机构信息

Clinical Neurobiology, Peninsula Medical School, University of Exeter, Exeter, UK.

出版信息

Methods Mol Biol. 2012;867:349-62. doi: 10.1007/978-1-61779-767-5_22.

DOI:10.1007/978-1-61779-767-5_22

PMID:22454072

Abstract

Many genetic mutations result in the disruption of (alternative) splicing. Prime examples are the SMN1 and SMN2 genes: a silent mutation in SMN2 leads to the skipping of the constitutive exon 7 in the majority of SMN2 transcripts, while this exon is generally included in SMN1 transcripts. Lack of SMN is embryonic lethal and loss of SMN1 genes leads to a severe decrease in SMN protein and is associated with spinal muscular atrophy. There are proteins and drugs that can chance alternative splicing events, e.g. increase the inclusion of exon 7 in SMN2. This chapter describes mini-genes and methods that can be employed to screen for candidate proteins and drugs.

摘要

许多基因突变会导致（选择性）剪接的破坏。典型的例子是SMN1和SMN2基因：SMN2中的一个沉默突变导致大多数SMN2转录本中组成型外显子7的缺失，而该外显子通常包含在SMN1转录本中。缺乏SMN是胚胎致死性的，SMN1基因的缺失会导致SMN蛋白严重减少，并与脊髓性肌萎缩症相关。有一些蛋白质和药物可以改变选择性剪接事件，例如增加SMN2中外显子7的包含。本章描述了可用于筛选候选蛋白质和药物的微型基因和方法。