生物
剪接
遗传学
RNA剪接
外显子
内含子
基因
人类基因组
选择性拼接
生物信息学
剪接位点突变
基因组
计算生物学
核糖核酸
作者
Ulrika Simone Spangsberg Petersen,Thomas Koed Doktor,Brage Storstein Andresen
摘要
Accuracy of pre-messenger RNA (pre-mRNA) splicing is crucial for normal gene expression. Complex regulation supports the spliceosomal distinction between authentic exons and the many seemingly functional splice sites delimiting pseudoexons. Pseudoexons are nonfunctional intronic sequences that can be activated for aberrant inclusion in mRNA, which may cause disease. Pseudoexon activation is very challenging to predict, in particular when activation occurs by sequence variants that alter the splicing regulatory environment without directly affecting splice sites. As pseudoexon inclusion often evades detection due to activation of nonsense-mediated mRNA decay, and because conventional diagnostic procedures miss deep intronic sequence variation, pseudoexon activation is a heavily underreported disease mechanism. Pseudoexon characteristics have mainly been studied based on in silico predicted sequences. Moreover, because recognition of sequence variants that create or strengthen splice sites is possible by comparison with well-established consensus sequences, this type of pseudoexon activation is by far the most frequently reported. Here we review all known human disease-associated pseudoexons that carry functional splice sites and are activated by deep intronic sequence variants located outside splice site sequences. We delineate common characteristics that make this type of wild type pseudoexons distinct high-risk sites in the human genome.
科研通智能强力驱动
Strongly Powered by AbleSci AI