de la Grange Pierre
GenoSplice technology, iPEPS - ICM, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
Med Sci (Paris). 2016 Dec;32(12):1111-1119. doi: 10.1051/medsci/20163212015. Epub 2017 Jan 3.
Most of protein-coding human genes are subjected to alternative pre-mRNA splicing. This mechanism is highly regulated to precisely modulate detection of specific splice sites. This regulation is under control of the spliceosome and several splicing factors are also required to modulate the alternative usage of splice sites. Splicing factors and spliceosome components recognize splicing signals and regulatory sequences of the pre-mRNAs. These splicing sequences make splicing susceptible to polymorphisms and mutations. Examples of associations between human rare diseases and defects in pre-messenger RNA splicing are accumulating. Although many alterations are caused by mutations in splicing sequence (i.e., cis acting mutations), recent studies described the disruptive impact of mutations within spliceosome components or splicing factors (i.e., trans acting mutations). Following growing of knowledge regarding splicing regulation, several approaches have been developed to compensate for the effect of deleterious mutations and to restore sufficient amounts of functional protein.
大多数人类蛋白质编码基因都经历可变前体信使核糖核酸（pre-mRNA）剪接。这种机制受到高度调控，以精确调节特定剪接位点的识别。这种调控由剪接体控制，还需要几种剪接因子来调节剪接位点的可变使用。剪接因子和剪接体成分识别前体信使核糖核酸的剪接信号和调控序列。这些剪接序列使剪接容易受到多态性和突变的影响。人类罕见疾病与前体信使核糖核酸剪接缺陷之间关联的例子正在不断积累。虽然许多改变是由剪接序列中的突变（即顺式作用突变）引起的，但最近的研究描述了剪接体成分或剪接因子内突变（即反式作用突变）的破坏性影响。随着对剪接调控知识的不断增加，已经开发了几种方法来补偿有害突变的影响并恢复足够数量的功能性蛋白质。
